CREATE TABLE IF NOT EXISTS neuropro_v1 (
    `Gene_Symbol` VARCHAR(8) CHARACTER SET utf8,
    `Full_Name` VARCHAR(64) CHARACTER SET utf8,
    `neuroprotective_and_or_neurotrophic_activity` ENUM('neurotrophic','neurotrophic/neuroprotective','no trophic/protective activity identified'),
    `in_vitro_evidence_DOI_PMID` VARCHAR(142) CHARACTER SET utf8,
    `in_vivo_evidence_DOI_PMID` VARCHAR(148) CHARACTER SET utf8,
    `condition_specific_effects_DOI_PMID` VARCHAR(79) CHARACTER SET utf8,
    `Supporting_sentences_in_vitro` VARCHAR(1644) CHARACTER SET utf8,
    `Supporting_sentences_in_vivo` VARCHAR(1653) CHARACTER SET utf8,
    `Supporting_sentences_condition_specific_effects` VARCHAR(1099) CHARACTER SET utf8
);
INSERT INTO neuropro_v1 VALUES
    ('BDNF','brain derived neurotrophic factor','neurotrophic/neuroprotective','10.1084/jem.189.5.865;10.1016/0896-6273(90)90166-D;10.3858/emm.2010.42.8.060;10.1002/neu.480250805','10.1002/dev.20546;10.1242/dev.008227;10.1006/mcne.1998.0684;10.1016/0896-6273(93)90326-M;10.1038/331261a0;10.1016/S0165-3806(98)00155-2;PMID:8656282',NULL,'The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro.;Brain-derived neurotrophic factor (BDNF) was found to promote the survival of Ell 7 rat embryo septal cholinergic neurons in culture, as assessed by a histochemical stain for acetylcholinesterase (AChE);Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.;In explants treated for 7 days, the actions of NT-4/5 were similar to those of brain-derived neurotrophic factor (BDNF)- with either neurotrophin, nearly twice as many RGCs survived and there was a two- to threefold increase in the number of neurites formed by RGCs.','We review what is known regarding the functional role of newly born cells, highlight the role of BDNF in this process, and describe preliminary findings from our lab implicating BDNF in the process of selecting of newly born cells for survival.;Inhibition of TrkB/C also caused a delay in the generation of neurons, but not astrocytes, and ultimately perturbed the postnatal localization of cortical neurons in vivo. Conversely, overexpression of BDNF in cortical precursors in vivo promoted proliferation and enhanced neurogenesis.;In both experimental paradigms we observed significantly more BrdU-labeled cells in the olfactory bulbs on the BDNF-infused side than in the olfactory bulb of PBS-infused animals.;Finally, BDNF prevents motor neuron death in the axotomized facial nucleus of the neonatal rat.;The generalization of the concept that neurotrophic proteins regulate neuronal survival during normal development critically depends on the demonstration that the survival of neurons in vivo can be increased by the administration of a neurotrophic protein different from NGF. We report here that this is the case with brain-derived neurotrophic factor, a protein of extremely low abundance purified from the central nervous system.;Analysis of motoneuron numbers indicated that both BDNF and GDNF provided protection to developing spinal cord motoneurons from ethanol toxicity, restoring motoneuron numbers to control levels.;These specific in vivo effects of BDNF and NT-4/5 on axonal regeneration from injured RGCs may be used to promote growth and expand the abnormally small terminal arbors observed when RGCs regrow into their CNS targets.',NULL),
    ('NGF','nerve growth factor','neurotrophic/neuroprotective','10.1126/science.3798108;10.3858/emm.2010.42.8.060:10.1038/jcbfm.1993.51','PMID: 10403429',NULL,'Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.;Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each protected neurons against iron-induced damage.','By using the nerve growth factor antisense oligonucleotide we could demonstrate that nerve growth factor mediated the neuroprotective effects of the beta2-adrenoceptor agonist clenbuterol in vitro and in vivo.',NULL),
    ('NTF3','neurotrophin 3','neurotrophic/neuroprotective','10.1016/j.neulet.2012.04.036','10.1038/367368a0;10.3727/096368909X477273',NULL,'Cultures treated with NT-3 prior to exposure showed reduced cell death compared to untreated control or GDNF-treated cultures.','The results show that NT-3, but no other neurotrophin, prevents the degeneration of noradrenergic neurons of the locus coeruleus in a 6-hydroxydopamine lesion model that resembles the pattern of cell loss found in Alzheimer''s disease;We report here that the combination of the NT-3, PDGF, and fibrin scaffold (with or without HBDS) enhanced the total number of ESNPCs present in the spinal cord lesion 2 weeks after injury.',NULL),
    ('NTF4','neurotrophin 4','neurotrophic','10.1002/neu.480250805','PMID:8656282',NULL,'In explants treated for 7 days, the actions of NT-4/5 were similar to those of brain-derived neurotrophic factor (BDNF)- with either neurotrophin, nearly twice as many RGCs survived and there was a two- to threefold increase in the number of neurites formed by RGCs.','These specific in vivo effects of BDNF and NT-4/5 on axonal regeneration from injured RGCs may be used to promote growth and expand the abnormally small terminal arbors observed when RGCs regrow into their CNS targets.',NULL),
    ('GDNF','glial derived neurotrophic factor','neurotrophic/neuroprotective','10.1126/science.8493557','10.1016/S0165-3806(98)00155-2;10.1016/0361-9230(94)00224-O','PMID:16838029','In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake.','The concurrent delivery of BDNF or GDNF with ethanol to the embryonic chick from E10 to E15 was designed to examine the capacity of these NTFs to provide in vivo neuroprotection for this ethanol-sensitive motoneuron population. Analysis of motoneuron numbers indicated that both BDNF and GDNF provided protection to developing spinal cord motoneurons from ethanol toxicity, restoring motoneuron numbers to control levels.;Using immunocytochemistry, we found sprouting of tyrosine hydroxylase-positive neurites towards the injection site, and increased tyrosine hydroxylase immunoreactivity of the ipsilateral striatum was produced by GDNF.','Long-lasting GDNF-mediated neuroprotection depended on BclX(L) co-expression in the traumatic lesion paradigm, but was independent of BclX(L) in the 6-OHDA lesion model.'),
    ('FGF1','fibroblast growth factor 1','neurotrophic','PMID:1941074;10.1046/j.1471-4159.2002.00837.x',NULL,NULL,'Treatment of these cultures with acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF) increased the number of surviving tyrosine hydroxylase-immunoreactive (TH-IR) neurons by 90-110% [corrected] at 8 d in vitro in a dose-dependent manner.;These data show that both SF/HGF and FGF-1 protect cerebellar granule neurons against excitotoxicity with similar potency in a PI3-K/Akt-dependent and MAP-kinase/CREB-independent manner.',NULL,NULL),
    ('EGF','epidermal growth factor','neurotrophic','10.1126/science.3498986;PMID:2406380','PMID:8076517',NULL,'In the present study, EGF was found to enhance survival and process outgrowth of primary cultures of subneocortical telencephalic neurons of neonatal rat brain in a dose-dependent manner.;Epidermal growth factor (EGF) produced a small increase in dopamine uptake by mesencephalic cells and stimulated cell proliferation in all culture types.','We also show that in vivo treatment with epidermal growth factor inhibits cell death in the developing kidney, consistent with the possibility that the cells normally die because they lack sufficient survival factors.',NULL),
    ('IGF1','insulin like growth factor 1','neurotrophic','PMID:9030615;PMID:2406380','PMID:10632601',NULL,'Cultured cerebellar granule neurons die by apoptosis when switched from a medium containing an elevated level of potassium (K+) to one with lower K+ (5 mM). Death resulting from the lowering of K+ can be prevented by insulin-like growth factor (IGF-1).;Insulin and the insulin-like growth factors I and II stimulated transmitter-specific differentiation and cell proliferation in all culture types.','Our results indicate that intraocular application of IGF-I protects RGCs from death after ON transection in a dose-dependent manner. We show reduced caspase-3 activity as one possible neuroprotective mechanism of IGF-I treatment in vivo.',NULL),
    ('PDGFA','platelet-derived growth factor A','no trophic/protective activity identified','10.1007/BF00229041',NULL,NULL,NULL,NULL,NULL),
    ('PDGFB','platelet-derived growth factor B','neurotrophic','PMID:1654560;10.1016/j.neuroscience.2004.11.056;10.1007/BF00229041','10.3727/096368909X477273',NULL,'Continuous PDGF-BB treatment of primary rat brain cell cultures resulted in outgrowth of neurites and prolonged survival.;The effects of i.c.v. infused platelet-derived growth factor and brain-derived neurotrophic factor on cell genesis, as assessed with bromodeoxyuridine (BrdU) incorporation, were studied in adult rats with unilateral 6-hydroxydopamine lesions. Both growth factors increased the numbers of newly formed cells in the striatum and substantia nigra to an equal extent following 10 days of treatment.;PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures.','We report here that the combination of the NT-3, PDGF, and fibrin scaffold (with or without HBDS) enhanced the total number of ESNPCs present in the spinal cord lesion 2 weeks after injury.',NULL),
    ('VEGFA','vascular endothelial growth factor','neurotrophic','10.1073/pnas.182296499;PMID:10407014;10.1046/j.0953-816X.2000.01326.x','10.1073/pnas.182296499',NULL,'VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.','Intracerebroventricular administration of VEGF into rat brain increased BrdUrd labeling of cells in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 was colocalized with the immature neuronal marker, doublecortin (Dcx).',NULL),
    ('VEGFB','vascular endothelial growth factor','neurotrophic','10.1073/pnas.182296499;PMID:10407014;10.1046/j.0953-816X.2000.01326.x','10.1073/pnas.182296499',NULL,'VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.','Intracerebroventricular administration of VEGF into rat brain increased BrdUrd labeling of cells in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 was colocalized with the immature neuronal marker, doublecortin (Dcx).',NULL),
    ('VEGFC','vascular endothelial growth factor','neurotrophic','10.1073/pnas.182296499;PMID:10407014;10.1046/j.0953-816X.2000.01326.x','10.1073/pnas.182296499',NULL,'VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.','Intracerebroventricular administration of VEGF into rat brain increased BrdUrd labeling of cells in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 was colocalized with the immature neuronal marker, doublecortin (Dcx).',NULL),
    ('VEGFD','vascular endothelial growth factor','neurotrophic','10.1073/pnas.182296499;PMID:10407014;10.1046/j.0953-816X.2000.01326.x','10.1073/pnas.182296499',NULL,'VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.','Intracerebroventricular administration of VEGF into rat brain increased BrdUrd labeling of cells in the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), where VEGFR2/Flk-1 was colocalized with the immature neuronal marker, doublecortin (Dcx).',NULL),
    ('CDNF','cerebral dopamine neurotrophic factor','neurotrophic/neuroprotective','10.1016/j.bbrc.2013.04.029','10.1038/nature05957;10.1016/j.expneurol.2010.12.013',NULL,'Our results show that the percentage of LDH released as a result of ER stress was significantly lower in astrocytes with an overexpression of CDNF than in the control groups without CDNF overexpression, indicating that CDNF alleviates ER stress-induced astrocyte damage. The secretion and mRNA expression levels of pro-inflammatory cytokines were increased by tunicamycin, and this stimulation was significantly suppressed by an overexpression of CDNF, demonstrating that CDNF plays an important role in astrocyte inflammation and functioning by resisting ER stress.','In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson’s disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra.;The amphetamine-induced rotational behavior was gradually normalized in rats treated with CDNF for two weeks following the intrastriatal 6-OHDA injection. CDNF was also able to inhibit 6-OHDA-induced loss of TH-immunoreactive cells of the SNpc and TH-positive fibers in the striatum.',NULL),
    ('MANF','mesencephalic astrocyte derived neurotrophic factor','neurotrophic','10.1385/JMN:20:2:173','10.1002/cne.22039;10.1523/JNEUROSCI.0833-09.2009',NULL,'Compared to glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), MANF was more selective in the protection of dopaminergic neurons at lower (0.05–0.25 ng/mL) and middle (0.5–2.5 ng/mL) concentrations: MANF>GDNF>BDNF.','Animals receiving MANF pretreatment demonstrated a decrease in body asymmetry and neurological score as well as an increase in locomotor activity after MCAo. Taken together, these data suggest that MANF has neuroprotective effects against cerebral ischemia, possibly through the inhibition of cell necrosis/apoptosis in cerebral cortex.; Intrastriatally injected MANF protected nigrostriatal dopaminergic nerves from 6-OHDA-induced degeneration as evaluated by counting tyrosine hydroxylase (TH)-positive cell bodies in the substantia nigra (SN) and TH-positive fibers in the striatum. More importantly, MANF also restored the function of the nigrostriatal dopaminergic system when administered either 6 h before or 4 weeks after 6-OHDA administration in the striatum.',NULL),
    ('NENF','neudesin neurotrophic factor','neurotrophic','10.1002/jnr.20356;10.1002/jnr.20849',NULL,'10.1074/jbc.M706679200','Mouse neudesin mRNA was expressed in neurons but not glial cells of the brain. The protein exhibited significant neurotrophic activity in primary cultured mouse neurons but not mitogenic activity in primary cultured mouse astrocytes.;Neudesin significantly promoted neuronal differentiation and overrode the undifferentiated state of the neural precursor cells sustained by fibroblast growth factor 2 (FGF2).',NULL,'The neurotrophic activity of the recombinant neudesin that bound exogenous hemin (neudesin-hemin) was significantly greater than that of the recombinant neudesin in either primary cultured neurons or Neuro2a cells, suggesting that the activity of neudesin depends on hemin.'),
    ('ARTN','artemin','neurotrophic','10.1016/S0896-6273(00)80649-2','10.1006/mcne.1999.0817',NULL,'Artemin is a survival factor for sensory and sympathetic neurons in culture, and its expression pattern suggests that it also influences these neurons in vivo. Artemin can also activate the GFRalpha1–RET complex and supports the survival of dopaminergic midbrain neurons in culture, indicating that like GDNF (GFRalpha1–RET) and NTN (GFRalpha2–RET), Artemin has a preferred receptor (GFRalpha3–RET) but that alternative receptor interactions also occur.','Three weeks after an intrastriatal 6-hydroxydopamine lesion only about 20% of the nigral DA neurons were left in the control group, while 80–90% of the DA neurons remained in the NBN/ART and GDNF treatment groups, and the striatal TH-immunoreactive innervation was partly spared. We conclude that NBN/ART, similarly to GDNF, is a potent neuroprotective factor for the nigrostriatal DA neurons in vivo.',NULL),
    ('NRTN','neurturin','neurotrophic','10.1006/mcne.1999.0756','10.1006/exnr.1999.7175',NULL,'Here, we report that neurturin, like GDNF, increases the choline acetyltransferase activity of normal postnatal motor neurons, induces neurite outgrowth in spinal cord, and potently protects motor neurons from chronic glutamate-mediated degeneration.','Amphetamine-induced activity levels were increased in both NTN- and GDNF-treated animals, with higher activity levels achieved by GDNF than NTN.',NULL),
    ('PSPN','persephin','neurotrophic','10.1016/S0896-6273(00)80453-5','10.1016/S0896-6273(00)80453-5',NULL,'Persephin, like GDNF and NTN, promotes the survival of ventral midbrain dopaminergic neurons in culture and prevents their degeneration after 6-hydroxydopamine treatment in vivo.','Persephin also supports the survival of motor neurons in culture and in vivo after sciatic nerve axotomy and, like GDNF, promotes ureteric bud branching.',NULL),
    ('HGF','hepatocyte growth factor','neurotrophic/neuroprotective','10.1046/j.1471-4159.2002.00837.x;10.1097/00004647-199804000-00001','PMID:11509947','10.1046/j.1471-4159.2002.00837.x','These data show that both SF/HGF and FGF-1 protect cerebellar granule neurons against excitotoxicity with similar potency in a PI3-K/Akt-dependent and MAP-kinase/CREB-independent manner.;Continuous postischemic intrastriatal administration of human recombinant HGF (10 or 30 µg) for 7 days potently prevented the delayed death of hippocampal neurons under both anesthetized and awake conditions.','To develop a novel strategy to prevent delayed neuronal death (DND) following transient occlusion of arteries, the gene of hepatocyte growth factor (HGF), a novel neurotrophic factor, was transfected into the subarachnoid space of gerbils after transient forebrain ischemia. Importantly, transfection of HGF gene into the subarachnoid space prevented DND, accompanied by a significant increase in HGF in the cerebrospinal fluid.','Neuroprotection against NMDA or QUIN by SF/HGF and FGF-1 was negated by the addition of LY294002 (10 µm) or wortmannin (100 nm), two distinct inhibitors of phosphatidylinositol 3-kinase (PI3-K), but not by the MAP-kinase kinase (MEK) inhibitor PD98059 (33 µm). Likewise, expression of a dominant-negative mutant of Akt (Akt-kd) completely prevented the neuroprotective actions of SF/HGF and FGF-1.'),
    ('ADNP','activity-dependent neuroprotector homeobox','neurotrophic/neuroprotective','10.1016/j.mce.2006.03.029','10.1124/jpet.107.129551',NULL,'Pre-incubation with VP22-ADNP enriched protein fractions protected against beta amyloid peptide toxicity and oxidative stress (H2O2) in PC12 cells. VP22 by itself was devoid of protective activity.','NAP (NAPVSIPQ) is a peptide derived from ADNP that interacts with microtubules and provides potent neuroprotection. NAP treatment partially ameliorated cognitive deficits and reduced tau hyperphosphorylation in the ADNP+/– mice.',NULL),
    ('METRNL','meteorin, glial cell differentiation regulator-like','neurotrophic/neuroprotective','10.1038/sj.emboj.7600202;PMID:22044868;10.1242/jcs.063784','PMID:22044868;10.3233/RNN-2012-110199',NULL,'Meteorin selectively promoted astrocyte formation from mouse cerebrocortical neurospheres in differentiation culture, whereas it induced cerebellar astrocytes to become radial glia. Meteorin also induced axonal extension in small and intermediate neurons of sensory ganglia by activating nearby satellite glia.;Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced apoptotic cell death in SVZ cells in vitro.;Here, we demonstrate that meteorin is involved in GFAP-positive glial differentiation through activation of the Jak-STAT3 pathway, by using neurosphere and retinal explant culture systems.','Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum.;Implant-delivered Meteorin effectively protected against QA-induced toxicity, as manifested by both near-normal neurological performance and reduction of brain cell death.',NULL),
    ('MDK','Midkine (Neurite Growth-Promoting Factor 2)','neurotrophic/neuroprotective','10.1016/0304-3940(93)90904-Y;PMID:8827451','10.1186/1471-2202-11-42;10.1038/sj.gt.3302434',' ','MK at the optimal concentration of 10 ng/ml promoted the survival of mouse mesencephalic neurons in culture as demonstrated by the increased number of microtubule-associated protein-2 (MAP2) immunostaining-positive and tyrosine hydroxylase immunostaining-positive neurons and an elevated uptake of radiolabeled dopamine.; To examine the neurite-guiding activity of MK, rat embryonic brain cells (embryonic days 17-18) were cultured on plates coated with purified MK in a grid pattern. The cells attached to and extended their neurites along the substrate pattern.','Concurrent injection of MK and KA attenuated KA-induced seizure activity and cell death of hippocampal neurons including pyramidal cells and glutamic acid decarboxylase 67 (GAD67)-positive GABAergic interneurons in the CA3 and hilar area.;TUNEL-positive and cleaved caspase-3-positive cells in the periischemic area of AdMK-treated rats were significantly fewer than those in Adbetagal-treated rats, suggesting that the reduction of infarct volume by midkine was partly mediated by its antiapoptotic action.',NULL),
    ('CHRNA7','cholinergic receptor nicotinic alpha 7 subunit','neurotrophic/neuroprotective','PMID:28890319;PMID:17493709','PMID:22624500','10.1016/j.neuropharm.2013.10.034','Using human neuroblastoma SH-SY5Y cells, we found that the neuroprotective function of CHRNA7 is blocked by CHRNA7 knockdown using RNA interference. [...] Furthermore, activation of CHRNA7 is neuroprotective both in vitro (Martin et al., 2004 Qi et al., 2007) and in vivo (Di Cesare Mannelli et al., 2014 Liu et al., 2012).;These findings indicate that alpha7 nAChR may play a significant neuroprotective role by enhancing cleavage of APP by alpha-secretase, regulating signal transduction, improving antioxidant defenses and inhibiting the toxicity of Abeta, which is connected with the pathogenesis of AD','Systemic administration of nicotine alleviated MPTP-induced behavioral symptoms, improved motor coordination, and protected against dopaminergic neuron loss and the activation of astrocytes and microglia in the substantia nigra. The protective effects of nicotine were abolished by administration of the a7-nAChR-selective antagonist methyllycaconitine (MLA).','In summary, a7 nAChR is involved in oxaliplatin-dependent neuropathology and the agonists (R)-ICH3 and PNU-282987 reduce pain and protect nervous tissue with concomitant glial activation.'),
    ('PINK1','PTEN induced putative kinase 1','neurotrophic/neuroprotective',NULL,'PMID:25611391',NULL,NULL,'More importantly, PINK1 ameliorated ATP levels, neuronal integrity and adult fly survival, demonstrating that PINK1 counteracts the neurotoxicity of mHtt.',NULL),
    ('BAG1','BCL2 associated athanogene 1','neurotrophic/neuroprotective','PMID:20156966;PMID:19712056',NULL,NULL,'We observed that this aberrant phenotype can be reversed by the expression of the cochaperone BAG1 (Bcl-2-associated athanogene 1), restoring DJ-1 subcellular distribution, dimer formation, and chaperone activity and ameliorating cell survival.; In summary, we present BAG1 as a therapeutic tool modulating key steps in htt toxicity in vitro and ameliorating htt toxicity in vivo.',NULL,NULL),
    ('STAT3','signal transducer and activator of transcription 3','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('AQP4','aquaporin 4','neurotrophic/neuroprotective','PMID:27057365;PMID:26433375',NULL,'PMID:28714415','The association of AQP4 and GLT-1 could greatly supplement previous research regarding neuroprotection against AD.;Currently, it has been suggested that AQP4 influences synaptic plasticity, and AQP4 deficiency may impair learning and memory, in part, through glutamate transporter-1 (GLT-1).',NULL,'To add to this, AQP4 could participate in the AD pathogenesis through affecting neurotrophic factor production.'),
    ('FOXO3','forkhead box O3','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('SHH','sonic hedgehog','neurotrophic/neuroprotective','PMID:9221786','PMID:11771942 ',NULL,'Using cultures derived from embryonic day 14.5 (E14. 5) rat ventral mesencephalon, we show that Shh is also trophic for dopaminergic neurons.','This is the first demonstration in vivo that Shh reduces behavioral deficits induced by intrastriatal 6-OHDA lesion and suggests that Shh may be useful in the treatment of disorders that affect the nigrostriatal system, such as PD.',NULL),
    ('TRPM2','transient receptor potential cation channel subfamily M member 2','no trophic/protective activity identified','PMID:27872485;PMID:21383889',NULL,NULL,'In conclusion, results suggest that DEX treatment reduces cerebral ischemia-induced oxidative stress, cell death, and intracellular Ca2+ signaling through inhibition of TRPM2 and TRPV1 in the rat hippocampus and DRG;Recent studies indicate that TRPM2, a member of the TRPM subfamily of Ca(2+)-permeant, non-selective cation channel, plays an important role in mediating cellular responses to a wide range of stimuli that, under certain situations, can induce cell death. ',NULL,NULL),
    ('TTR','transthyretin','neurotrophic/neuroprotective','PMID:21880910 ',NULL,'PMID:27518433','In complementary tissue culture experiments, recombinant human TTR suppressed the cytotoxicity of soluble Aß aggregates added to mouse neurons and differentiated human SH-SY5Y neuroblastoma cells.',NULL,'TTR neuroprotection in vivo (pMCAO) is also megalin-dependent.'),
    ('SLPI','secretory leukocyte peptidase inhibitor','neurotrophic/neuroprotective',NULL,'PMID:23516280;PMID:20047904',NULL,NULL,'We also show that SLPI can overcome inhibition by CNS myelin and significantly enhance regeneration of transected retinal ganglion cell axons in rats.;We show, using transgenic mice over-expressing secretory leukocyte protease inhibitor, that this molecule has an early protective effect after spinal cord contusion injury.',NULL),
    ('SAG','S-antigen visual arrestin','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('TRH','thyrotropin releasing hormone','neurotrophic/neuroprotective','PMID:24199031',NULL,NULL,'TRH and its synthetic analogs have been recognized as trophic factors in neurons of the diencephalon and spinal cord, and as neuroprotectants against oxidative stress, glutamate toxicity, caspase-induced cell death, DNA fragmentation, and inflammation.',NULL,NULL),
    ('AVP','arginine vasopressin','neurotrophic/neuroprotective',NULL,'PMID:15266902',NULL,NULL,'This study suggests that neurohypophyseal hormone, AVP is neuroprotective against MgCl2 induced cerebral ischemia and this effect is modulated by PI-3 kinase enzyme inhibitors and protein kinase C inhibitors through possible influence on the cerebral vascular tone.',NULL),
    ('AIDA','axin interactor, dorsalization associated','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('LBP','lipopolysaccharide binding protein','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('CAST','calpastatin','neurotrophic/neuroprotective','PMID:22897874;PMID:21219955','PMID:22843411;PMID:16467455;PMID:12764095',NULL,'Supplementation of cells with exogenous calpastatin was able to reverse the toxic effect of METH on reduction in cell viability and tyrosine hydroxylase phosphorylation.;Ab-toxicity was attenuated in the high calpastatin-containing NDMh-infected cells, as shown by inhibition of calpain activation and activity, no membrane permeability, normal cell morphology, and maintenance of mitochondrial enzyme activity (similar to attenuation of Ab-toxicity in non-infected cells overexpressing calpastatin following calpastatin-plasmid introduction into the cells).','For this purpose, we inhibited calpain activity in mouse models of Machado–Joseph disease by overexpressing the endogenous calpain-inhibitor calpastatin. Calpain blockage reduced the size and number of mutant ataxin 3 inclusions, neuronal dysfunction and neurodegeneration.;Taken together, both inhibition of caspase-3-induced calpastatin degradation and calpain-induced fodrin breakdown by DY-9760e in part mediate its neuroprotective action.;Inhibition of calpain proteolysis using either a calpain inhibitor (MDL-28170) or adenovirus-mediated overexpression of the endogenous calpain inhibitor protein, calpastatin, significantly attenuated MPTP-induced loss of nigral dopamine neurons.',NULL),
    ('NMNAT2','nicotinamide nucleotide adenylyltransferase 2','neurotrophic/neuroprotective','PMID:27254664','PMID:20857515;PMID:22027994;PMID:27254664',NULL,'Taken together, our data indicate that NMNAT2 exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health.','Here we demonstrated that overexpression of Nmnat2 in M-cells significantly delayed axon degeneration in vivo, and disruption of the NAD synthesis activity of Nmnat2 markedly attenuated its axon-protective function.;In summary, our studies strongly support a protective role of NMNAT2 in the mammalian central nervous system.;Taken together, our data indicate that NMNAT2 exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health.',NULL),
    ('AK7','adenylate kinase 7','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('HTRA2','HtrA serine peptidase 2','neurotrophic/neuroprotective',NULL,'PMID:14534547;PMID:15509788',NULL,NULL,'The neurodegeneration and juvenile lethality in mnd2 mice result from this defect in mitochondrial Omi protease.;We report here the phenotype of mice entirely lacking expression of HtrA2/Omi due to targeted deletion of its gene, Prss25. These animals, or cells derived from them, show no evidence of reduced rates of cell death but on the contrary suffer loss of a population of neurons in the striatum, resulting in a neurodegenerative disorder with a parkinsonian phenotype that leads to death of the mice around 30 days after birth.',NULL),
    ('AGTR2','angiotensin II receptor type 2','neurotrophic/neuroprotective','PMID:23174180','PMID:19246705;PMID:24849663;PMID:23174180',NULL,'Our data suggest that selective AT2R-stimulation improves functional recovery in experimental spinal cord injury through promotion of axonal plasticity and through neuroprotective and anti-apoptotic mechanisms.','Thus, for the first time, we have shown that central AT2R stimulation is neuroprotective in a conscious rat model of stroke;In conclusion, AT2 is involved in HA-mediated neuroprotection, and AT2 activation may be protective and should be considered a novel drug target in the treatment of TBI patients.;Our data suggest that selective AT2R-stimulation improves functional recovery in experimental spinal cord injury through promotion of axonal plasticity and through neuroprotective and anti-apoptotic mechanisms.',NULL),
    ('APP','amyloid beta precursor protei','neurotrophic',NULL,'PMID:29478851;PMID:29426354','PMID:29478851;PMID:29426354',NULL,'Moreover, expression of sAPPa in APP-deficient mice could rescue their deficits in learning, spatial memory, and long-term potentiation [2]. Loss of the Drosophila APP-like (APPL) protein impairs associative olfactory memory formation and middle-term memory that can be rescued with a secreted APPL fragment;Together these findings suggest that sAPPa has wide potential to act as either a preventative or restorative therapeutic treatment in AD by mitigating the effects of Aß toxicity and enhancing cognitive reserve.','Moreover, expression of sAPPa in APP-deficient mice could rescue their deficits in learning, spatial memory, and long-term potentiation [2]. Loss of the Drosophila APP-like (APPL) protein impairs associative olfactory memory formation and middle-term memory that can be rescued with a secreted APPL fragment;Together these findings suggest that sAPPa has wide potential to act as either a preventative or restorative therapeutic treatment in AD by mitigating the effects of Aß toxicity and enhancing cognitive reserve.'),
    ('VGF','VGF nerve growth factor inducible','neurotrophic','PMID:28287464',NULL,NULL,'Taken together, our results suggest VGF enhances dendritic maturation and that these effects can be altered by common mutations in the VGF gene.',NULL,NULL),
    ('ADAM10','ADAM metallopeptidase domain 10','neurotrophic/neuroprotective','PMID:10097139;PMID:20676056','PMID:15146243',NULL,'Our results provide evidence that ADAM 10 has alpha-secretase activity and many properties expected for the proteolytic processing of APP. Increases of its expression and activity might be beneficial for the treatment of Alzheimer''s disease.;The amyloid precursor protein (APP) undergoes constitutive shedding by a protease activity called a-secretase. This is considered an important mechanism preventing the generation of the Alzheimer’s disease amyloid-b peptide (Ab) [...] We conclude that ADAM10 is the physiologically relevant, constitutive alpha-secretase of APP.','In this report we show that a moderate neuronal overexpression of ADAM10 in mice transgenic for human APP[V717I] increased the secretion of the neurotrophic soluble a-secretase–released N-terminal APP domain (APPsa), reduced the formation of Aß peptides, and prevented their deposition in plaques. Functionally, impaired long-term potentiation and cognitive deficits were alleviated. Expression of mutant catalytically inactive ADAM10 led to an enhancement of the number and size of amyloid plaques in the brains of double-transgenic mice.',NULL),
    ('GALR2','galanin receptor 2','neurotrophic/neuroprotective',NULL,'PMID:16487144;PMID:15041741;PMID:19717462;PMID:22624057',NULL,NULL,'These data are in line with earlier observations from the peripheral and central nervous system, suggesting that galanin actions mediated by GalR2 subtype are of importance in neurodevelopment and neuroprotection.;Further, exogenous galanin or the previously described high-affinity GALR2 agonist, both reduced cell death when coadministered with glutamate or staurosporine in WT cultures. These results demonstrate that galanin acts an endogenous neuroprotective factor to the hippocampus and imply that a galanin agonist might have therapeutic uses in some forms of brain injury.;The pronounced effects of altered endogenous galanin or GalR2 expression on EAE disease activity may reflect a direct neuroprotective effect of the neuropeptide via activation of GalR2, similar to that previously described in a number of neuronal injury paradigms.;These findings imply that Gal, via activation of GalR1 and/or GalR2, may have neuroprotective effects in reducing neuropathic pain behaviors and improving nerve regeneration after nerve injury.',NULL),
    ('SIRT1','sirtuin 1','neurotrophic/neuroprotective','PMID:23293585;PMID:22179319;10.1155/2017/2823454','PMID:22179319',NULL,'Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress.;These findings show a neuroprotective role for Sirt1 in mammalian Huntington’s disease models and open new avenues for the development of neuroprotective strategies in Huntington’s disease;These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA-induced neurotoxicity.','These findings show a neuroprotective role for Sirt1 in mammalian Huntington’s disease models and open new avenues for the development of neuroprotective strategies in Huntington’s disease.',NULL),
    ('CX3CR1','C-X3-C motif chemokine receptor 1','neurotrophic/neuroprotective',NULL,'PMID:16732273;PMID:22072684','PMID:22072684',NULL,'Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability;The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia [...] In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1-/- and cx3cr1(GFP/GFP) mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1-/- ischemic mice.','The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia [...] In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1-/- and cx3cr1(GFP/GFP) mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1-/- ischemic mice.'),
    ('SIRT2','sirtuin 2','no trophic/protective activity identified','PMID:17588900;PMID:29654491;PMID:25608039','PMID:17588900;PMID:29654491;PMID:16732273;PMID:22072684;PMID:25461978;PMID:25608039','PMID:25608039','Genetic inhibition of SIRT2 via small interfering RNA similarly rescued a-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson''s disease.;In summary, the current study demonstrated the neuroprotective effects of SIRT2 inhibition in ischemic stroke, and identified the downregulation of AKT/FOXO3a and MAPK pathways as intermediary mechanisms which may contribute to the reduction in apoptotic cell death by SIRT2 inhibition.; The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia.','Genetic inhibition of SIRT2 via small interfering RNA similarly rescued a-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson''s disease.;In summary, the current study demonstrated the neuroprotective effects of SIRT2 inhibition in ischemic stroke, and identified the downregulation of AKT/FOXO3a and MAPK pathways as intermediary mechanisms which may contribute to the reduction in apoptotic cell death by SIRT2 inhibition.; Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability;The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia [...] In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1-/- and cx3cr1(GFP/GFP) mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1-/- ischemic mice.; CX3CR1 antibody treatment resulted in a reduction in microglial activation, neurodegeneration, as well as neuroblast production.;The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia.','The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia.'),
    ('XBP1','X-box binding protein 1','neurotrophic/neuroprotective',NULL,'PMID:29518365;PMID:28487326;PMID:17890727;PMID:27646263;PMID:28726788','PMID:28726788',NULL,'In summary, the upregulation of RACK1 following brain contusion exerted neuroprotective effects against secondary brain injury, which were probably mediated by activation of the IRE1-XBP1 pathway.; Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent.;BDNF-dependent neurite outgrowth was significantly attenuated in Xbp1(-/-)  neurons. These findings suggest that BDNF initiates UPR signaling in neurites and that Xbp1, which is activated as part of the UPR, conveys the local information from neurites to the nucleus, contributing the neurite outgrowth.;Hence, our findings reveal that XBP1s is neuroprotective through a mechanism that engages Kal7 pathway with therapeutic implications in AD pathology.;Using this in vivo model, we now show that ER stress is induced early in EAE and that modulation of ER stress by inhibition of eIF2a-CHOP and activation of XBP-1 in RGC specifically, protects RGC somata and axons and preserves visual function.','Using this in vivo model, we now show that ER stress is induced early in EAE and that modulation of ER stress by inhibition of eIF2a-CHOP and activation of XBP-1 in RGC specifically, protects RGC somata and axons and preserves visual function.'),
    ('CRH','corticotropin releasing hormone','neurotrophic/neuroprotective','PMID:12933679','PMID:23380766;PMID:18708129',NULL,'Using primary neuronal cultures from the cerebellum, cerebral cortex, and hippocampus, we demonstrate that CRH exerts a brain region-specific neuroprotective effect on amyloid beta 25–35 toxicity.','Accordingly, we found that CRH could reverse the damaging effects of glucocorticoid on neural stem/progenitor cells (NS/PCs), while its genetic deficiency results in compromised proliferation and enhanced apoptosis during neurogenesis.;Our findings highlight a neuroprotective action of CRH in vivo.',NULL),
    ('MT3','metallothionein 3','neurotrophic/neuroprotective','10.1016/S0304-4165(02)00325-2;10.1080/09553000050051025;10.1016/S0006-8993(03)02633-7;10.1006/bbrc.2001.4594;10.1016/j.molbrainres.2004.09.011',NULL,NULL,'T-III was also able to efficiently remove the superoxide anion, which was generated from the xanthine/xanthine oxidase system. These results strongly suggest that MT-III is involved in the protection of reactive oxygen species-induced DNA damage, probably via direct interaction with reactive oxygen species, and that MT-III acts as a neuroprotective agent.;Furthermore, induction of MT synthesis with Zn and Cd can protect human CNS cells from radiation-induced cytocidal and sublethal injuries.;Among MTs, a brain-predominant subtype MT-III has prominent neuroprotective activity against various types of damage. Here we show that the expression of MT-III is induced in cultured normal human astrocytes by hypoxia, and that overexpressed MT-III protects human embryonic kidney cells from hypoxia, suggesting that MT-III can protect the brain from hypoxic damage.;Metallothionein-III (MT-III) protects cerebral cortical neurons in established culture from the toxic effect of amyloid ß peptides (Aßs).;MT-3 overexpression in these cells also significantly suppressed MPP+- and salsolinol-induced apoptosis.',NULL,NULL),
    ('CXCR4','C-X-C motif chemokine receptor 4','neurotrophic/neuroprotective',NULL,'10.1016/j.jns.2012.01.001;10.1002/ana.21919',NULL,NULL,'CXCR4 overexpression in the rMSCs promoted their mobilization and enhanced neuroprotection in a rat cerebral ischemia model.;Our data also showed that blocking CXCR4 on EPCs abolished the EPC-induced neuroprotection, suggesting that SDF-1/CXCR4 played a crucial role in EPC-mediated brain protection.',NULL),
    ('CPE','carboxypeptidase E','neurotrophic/neuroprotective','PMID:18570185;PMID:18550819;10.1210/en.2013-1118',NULL,NULL,'Ex vivo studies showed that overexpression of CPE in cultured hippocampal neurons protected them against H(2)O(2) oxidative-stress induced cell death.;Reducing CPE by approximately 30% using shRNA also increased ER stress and apoptosis. Conversely, overexpression of CPE partially rescued beta-cells from palmitate-induced ER stress and apoptosis.;Overexpression of CPE in hippocampal neurons, or CRS in mice, resulted in elevated prosurvival BCL2 protein/mRNA and p-AKT levels in the hippocampus, however, CPE-/- mice showed a decrease. Thus, during mild CRS, CPE expression is up-regulated, possibly contributed by glucocorticoids, to mediate neuroprotection of the hippocampus by enhancing BCL2 expression through AKT signaling, and thereby maintaining allostasis.',NULL,NULL),
    ('KDR','kinase insert domain receptor','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('OPTN','optineurin','no trophic/protective activity identified','10.1038/eye.2011.309',NULL,NULL,'On the contrary, Koga et al73 recently showed that overexpression of wild-type OPTN results in increased apoptosis of RGCs and that OPTN (wild type or the E50K mutant form), unlike MYOC, is devoid of effects on neurite outgrowth in neuronal cells.',NULL,NULL),
    ('TIMP3','TIMP metallopeptidase inhibitor 3','neurotrophic/neuroprotective','PMID:26299440','PMID:26299440',NULL,'Herein we demonstrate that tissue inhibitor of matrix metalloproteinase-3 (TIMP3), a soluble protein released by MSCs, is neuroprotective and enhances neuronal survival and neurite outgrowth in vitro.','In vivo in a murine model of TBI, intravenous recombinant TIMP3 enhances dendritic outgrowth and abrogates loss of hippocampal neural stem cells and mature neurons.',NULL),
    ('YY1','YY1 transcription factor','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('PTHLH','parathyroid hormone like hormone','neurotrophic/neuroprotective','10.1074/jbc.272.22.14404;10.1016/S0006-8993(01)03407-2','10.1016/S0006-8993(01)03407-2;10.1152/ajpregu.00436.2002',NULL,'PTHrP mRNA was persistently expressed before and after the time of commitment of granule neurons to apoptosis when they are cultured in the presence of 25 mMKCl or both 150 uM N-methyl-D-aspartic acid and 15 mMKCl, both of which promote the survival of these neurons. [...]  The addition of anti-PTHrP antiserum to the culture medium resulted in a reduction of the activity-dependent survival of the granule neurons.;PTHrP-null embryonic mixed cerebral cortical cultures were more sensitive to kainic acid than control cultures, and PTHrP addition was found to be protective against kainate toxicity in both PTHrP-null and control cultures.','Here, we tested the idea that mice with a PTHrP-null CNS might display hypersensitivity to kainic acid excitotoxicity. We found that these mice were six-fold more sensitive than control littermate mice to kainic-acid-induced seizures as well as hippocampal c-Fos expression.;Superfusion with PTHrP(1–34) peptide for up to 25 min increased pial arteriolar diameter by 30% in normal animals. In animals with permanent MCAO, PTHrP(1–34) peptide treatment significantly decreased cortical infarct size (47%).',NULL),
    ('GAP43','growth associated protein 43','neurotrophic/neuroprotective',NULL,NULL,'10.1038/cdd.2008.188;10.1002/(SICI)1097-4547(19970315)47:6<561::AID-JNR1>3.0.CO',NULL,NULL,'Using cortical cultures from GAP-43 knockout and control mice, we show that (1) GAP-43 is upregulated in response to S18986 and BDNF in control cultures, (2) this upregulation of GAP-43 is essential for mediating the neuroprotective effects of S18986 and BDN, (3) administration of S18986 and BDNF leads to an increase in the expression of the glutamate transporters GLT-1 and GLAST that are key to limiting excitotoxic cell death and this increase in GLT-1 and GLAST expression is completely blocked in the absence of GAP-43. Taken together this study concludes that GAP-43 is an important mediator of the neurotrophic effects of S18986 and BDNF on neuronal survival and plasticity, and is essential for the success of positive AMPA receptor modulator-BDNF-based neurotrophin therapy.;We conclude that BDNF specifically enhances GAP-43 but not Ta1 mRNA levels in injured RGCs. Because BDNF is known to stimulate branch length of injured RGCs, we suggest that changes in the expression of GAP-43, but not Ta1 tubulin, correlate with branching of injured neurons as opposed to long distance regrowth.'),
    ('NTRK3','neurotrophic receptor tyrosine kinase 3','neurotrophic',NULL,NULL,'10.1038/nrd4024',NULL,NULL,'However, in double mutant mice, we now show that reducing the expression of both TrkB and TrkC causes massive cell death of postnatal hippocampal and cerebellar granule neurons. [...] These findings indicate that TrkB and TrkC receptors cooperate in promoting the survival of dentate gyrus neurons in the postnatal brain.'),
    ('FGF9','fibroblast growth factor 9','neurotrophic/neuroprotective','10.1111/j.1471-4159.2009.06061.x;10.1016/j.freeradbiomed.2010.06.026;10.1016/S1044-7431(03)00070-8','10.1111/j.1471-4159.2009.06061.x',NULL,'In the absence of MPP+, the treatment of FGF9-neutralizing antibody-induced DA neuronal apoptosis whereas FGF9 protein reduced it indicating that endogenous FGF9 is a survival factor for DA neurons. We conclude that MPP+ down-regulates FGF9 expression to cause DA neuron death and that the prevention of FGF9 down-regulation is involved in melatonin-provided neuroprotection.;Simultaneous treatment with FGF9 and MPP+ prevented MPP+-induced neuron death and H2O2 overproduction but did not affect the FGF9-increased a-GCS and HO-1 protein expression.[...] These results indicate that FGF9 upregulates a-GCS and HO-1 expression to protect cortical and dopaminergic neurons from MPP+-induced oxidative insult.;Expression of each FGFR and effects of the preferred ligand for FGFR-3, FGF9, upon RGC survival and neurite outgrowth were examined in primary retinal cell cultures: whereas there was no stimulation of neuritogenesis, RGC survival was promoted in a dose-dependent manner (ED50 500 pg/ml, mean maximal increase of 60%) and could be completely blocked by addition of FGF9 neutralising antibody.','Treating neurons in the substantia nigra and mesencephalic cell cultures with FGF9 protein inhibited the MPP+-induced cell death of DA neurons. Melatonin co-treatment attenuated MPP+-induced FGF9 down-regulation and DA neuronal apoptosis in vivo and in vitro.',NULL),
    ('PRL','prolactin','neurotrophic','10.1016/j.neuroscience.2006.12.053','PMID:21507086',NULL,'Unlike growth hormone, central treatment with prolactin failed to rescue neurons in this paradigm. This was confirmed in vitro, rat prolactin failed to protect neurons under conditions for which growth hormone was neuroprotective. However, prolactin had trophic and pro-proliferative effects on glia (P<0.001).','Indeed, PRL administration to ovariectomised rats significantly diminishes the deleterious effects of KA in the dorsal hippocampus and reduces the progression of KA-induced seizures.',NULL),
    ('SORT1','sortilin 1','neurotrophic',NULL,'10.1016/j.tins.2012.03.007','10.1038/nn.2689',NULL,'For instance, blocking p75NTR signaling with neutralizing antibodies prevented the death of corticospinal neurons after axotomy. A comparable result has also been obtained in sortilin knockout mice, thus implicating pro-neurotrophins in this effect.','Moreover, deficiency for sortilin markedly aggravated TrkA, TrkB and TrkC phenotypes present in p75NTR knockouts, and resulted in increased embryonic lethality and sympathetic neuropathy in mice heterozygous for TrkA. Our findings demonstrate a role for sortilin as an anterograde trafficking receptor for Trk and a positive modulator of neurotrophin-induced neuronal survival.'),
    ('NLK','nemo like kinase','no trophic/protective activity identified','10.1007/s12031-013-0191-5;PMID:19840224;10.1371/journal.pone.0069148',NULL,NULL,'Coimmunoprecipitation data demonstrated that overexpression of NLK protein reduced ß-catenin binding to LEF-1. Our results suggested that NLK was associated with neuronal apoptosis through attenuating the Wnt/ß-catenin signaling pathway after SCIs.;Activated NLK directly phosphorylates microtubule-associated protein-1B (MAP1B) and the focal adhesion adaptor protein, paxillin. Knockdown of NLK attenuates the phosphorylation of both paxillin and MAP1B and inhibits both the NGF-induced re-distribution of F-actin and neurite outgrowth.;NLK suppressed proliferation, induced apoptosis and mediated c-Myb degradation in MCF-7 cells via a mechanism that seems to involve c-myc and Bcl2.',NULL,NULL),
    ('CARTPT','CART prepropeptide','neurotrophic','10.1016/j.bbrc.2006.06.117','PMID:21756347',NULL,'CART peptide promotes the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor','Cocaine- and amphetamine-regulated transcript promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells into neural cells',NULL),
    ('GJA1','gap junction protein alpha 1','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('CALCA','calcitonin related polypeptide alpha','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('GRN','granulin precursor','neurotrophic/neuroprotective','PMID:18378771;PMID:21820214;PMID:21204008',NULL,NULL,'Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival […] PGRN/GRN is a neurotrophic factor with activities that may be involved in the development of the nervous system and in neurodegeneration […] The full-length precursor, PGRN, exerted similar neurotrophic properties, both in motor and cortical neurons (Fig. 2, E and F). The maximal effect observed was a 38.5 and 22.0% increase in neuronal survival for motor and cortical neurons, respectively. ;Extracellular progranulin protects cortical neurons from toxic insults by activating survival signaling. […] ERK1/2 and Akt signaling mediate the neuroprotective activities of PGRN against MPP+ toxicity;Progranulin promotes neurite outgrowth and neuronal differentiation by regulating GSK-3ß […] PGRN induces neurite outgrowth in primary cultures of mouse cortical neurons.',NULL,NULL),
    ('ALS2','ALS2, alsin Rho guanine nucleotide exchange factor','neurotrophic/neuroprotective','PMID:16049005;PMID:16802292','PMID:16107644',NULL,'ALS2/Alsin Regulates Rac-PAK Signaling and Neurite Outgrowth [...] ALS2 promotes neurite outgrowth in cultured rat cortical neurons.;Alsin/Rac1 signaling controls survival and growth of spinal motoneurons. ','Loss of ALS2 Function Is Insufficient to Trigger Motor Neuron Degeneration in Knock-Out Mice But Predisposes Neurons to Oxidative Stress',NULL),
    ('EP300','E1A binding protein p300','neurotrophic','PMID:21705428;PMID:27256286','PMID:23804093',NULL,'The histone acetyltransferase p300 promotes intrinsic axonal regeneration […] p300 induces axonal regeneration and modifies the epigenome on select proregeneration promoters […] ;A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson’s Disease','A Novel Activator of CBP/p300 Acetyltransferases Promotes Neurogenesis and Extends Memory Duration in Adult Mice […] CBP/p300 activation favors differentiation of newly generated neurons in the dorsal hippocampus',NULL),
    ('NGB','neuroglobin','neurotrophic/neuroprotective','PMID:25023896;PMID:21915648','PMID:22167093;PMID:22703519',NULL,'TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen–glucose deprivation via the Jak2/Stat3 pathway in vitro […] Neuroglobin-mediated neuroprotection rescued cultured cells from OGD […] Our results demonstrate that TAT–Ngb can protect neuron-like cells against OGD-induced apoptosis by activating the Jak2/Stat3 pathway; Neuroprotective effects of neuroglobin after mechanical injury [...] Over-expressed NGB in injured B104 cells showed significant neuro- protective effects. Lactate dehydrogenase activity decreased and cell survival rates increased. Moderate and severe injuries had a higher NGB level than that in mild injury.','Neuroglobin overexpression plays a neuroprotective role against retinal ischemia reperfusion injury due to decreasing of mitochondrial oxidative stress-mediated apoptosis;Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress.',NULL),
    ('ADCYAP1','adenylate cyclase activating polypeptide 1','neurotrophic/neuroprotective','PMID:16805827;PMID:16004991;PMID:21524257 ','PMID:15084446;PMID:15518897;PMID:21524257 ',NULL,'The neurotrophic effects of PACAP in PC12 cells: control by multiple transduction pathways;PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone.;summarizes the findings on the neuroprotective potential of PACAP in models of neurodegenerative diseases, with special focus on in vitro and in vivo models of Parkinson`s disease, Huntington chorea and Alzheimer`s disease','Pituitary adenylate cyclase activating polypeptide protects dopaminergic neurons and improves behavioral deficits in a rat model of Parkinson''s disease.; Morphological and functional effects of PACAP in 6-hydroxydopamine-induced lesion of the substantia nigra in rats. [ …] Tyrosine-hydroxylase (TH) immunohistochemistry revealed increased number of dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area in all PACAP-treated rats in contrast to the severe cell loss in control animals.;summarizes the findings on the neuroprotective potential of PACAP in models of neurodegenerative diseases, with special focus on in vitro and in vivo models of Parkinson`s disease, Huntington chorea and Alzheimer`s disease',NULL),
    ('ATG12','autophagy related 12','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('ADORA1','adenosine A1 receptor','neurotrophic/neuroprotective','PMID:9221954',NULL,NULL,'The adenosine A1 binding enhancer PD 81,273 provided significant neuroprotection against hypoxic-ischemic brain injury in newborn rats. Because PD 81,273 selectively potentiates ADO A1 receptor activation in hypoxic tissues, this protective agent may produce fewer side effects than those seen with ADO A 1 receptor agonists and nonselective ADO receptor potentiating agents. ',NULL,NULL),
    ('NPAS4','neuronal PAS domain protein 4','neurotrophic/neuroprotective','PMID:26661154;PMID:24887558','PMID:26661154;PMID:26661154;PMID:24887558',NULL,'Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia […] Npas4, whose expression is robustly and transiently upregulated in the brain during the acute phase of ischaemia, plays a neuroprotective role because Npas4 deficiency increased the susceptibility of cultured neurons to cell death by OGD and exacerbated the severity of brain injury after photochemically-induced stroke in mice.;Reduced Npas4 expression during neural differentiation results in delayed neural differentiation','In this study, we used a loss-of-function approach to examine the neuroprotective potential of Npas4 in the context of ischaemic damage. Using oxygen and glucose deprivation, we demonstrated that the knockdown of Npas4 in mouse cortical neurons resulted in increased susceptibility to cell death. The protective effect of Npas4 was further investigated in vivo using a photochemically-induced stroke model in mice. We found a significantly larger lesion size and increased neurodegeneration in Npas4 knockout mice as compared to wild-type mice […] Taken together, these data suggest that Npas4 plays a neuroprotective role in ischaemic stroke by limiting progressive neurodegeneration and neuroinflammation.;Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia […] Npas4, whose expression is robustly and transiently upregulated in the brain during the acute phase of ischaemia, plays a neuroprotective role because Npas4 deficiency increased the susceptibility of cultured neurons to cell death by OGD and exacerbated the severity of brain injury after photochemically-induced stroke in mice.; Reduced Npas4 expression during neural differentiation results in delayed neural differentiation',NULL),
    ('INS','insulin','neurotrophic/neuroprotective','10.1016/j.jalz.2013.05.1140;PMID:3045261;PMID:12808000','PMID:19203442 ','PMID:10690636 ','Neuroprotective effects of insulin against H2O2-induced oxidative stress in primary hippocampal cell culture […] Results shows that 12 and 24 hour after exposure to 50, 100 and 150 uM H2O2, significant neuronal damage and cell death was evident both in morphological and MTT analysis, while 0.5 uM insulin was not effective enough to prevent these damages, when primary hippocampal neurons were pretreated with 1 M insulin, neuronal damage induced by 50 and 100 uM H2O2 was prevented while this dose of insulin was not able to prevent neuronal damage induced by 150 uM H2O2.;The present study also indicates that insulin fails to stimulate glucose oxidation and glycogen syn- thase activity in neurons. On the other hand, insulin does promote the survival and differentiation of fetal chick neurons in culture. This trophic effect was observed at low concentrations of insulin (10 ng/ml) and was dependent on the continuous presence of insulin in the medium. The number of neurons surviving in the presence of insulin was fewer than the number in serum, suggesting that only a specific population of neurons is supported by insulin;Neuronal necrosis inhibition by insulin through protein kinase C activation.','proximal elements of a known cell-survival pathway are triggered by high-dose insulin during early reperfusion. Insulin induces robust PI3K-dependent phosphorylation of Akt by 30 minute reperfusion and results in improvement of hippocampal structure and function. ','While effectively attenuating neuronal apoptosis in mouse cortical culture, insulin paradoxically induced neuronal necrosis with 48 h of exposure. […] The present study suggests that insulin can be both neuroprotective and neurotoxic in the same cell system but by way of different signaling cascades'),
    ('SYT10','synaptotagmin 10','neurotrophic/neuroprotective','PMID:26936998',NULL,NULL,'Syt10 knock-out neurons are more susceptible to KA-induced cell death […] Syt10 is a neuroprotective downstream effector of NPAS4 in activity-induced neuronal cell death',NULL,NULL),
    ('PHB','prohibitin','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('NTRK1','neurotrophic receptor tyrosine kinase 1','neurotrophic',NULL,'PMID:11756477',NULL,NULL,'TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal […] The results described in this paper indicate that p75NTR provides an apoptotic signal for developing sympathetic neurons in the presence or absence of TrkA, and one of the major ways that TrkA supports neuronal survival is by suppressing this death signal. […] the data reported here support a model of naturally occurring neuronal death where an ongoing, receptor-mediated apoptotic signal destines cells to die, and where one of the major roles of exogenous survival ligands is to silence this ongoing apoptotic signal. In the case of sympathetic neurons, p75NTR provides the death signal and TrkA the survival signal. ',NULL),
    ('DUSP6','dual specificity phosphatase 6','neurotrophic/neuroprotective','PMID:15530650',NULL,NULL,'Further analysis using realtime RT-PCR confirmed that we had identified genes that are regulated by single growth factors, as well as several more that are co-regulated by both IGF-1 and bFGF. These genes can influence neuronal survival by affecting diverse pathways such as growth factor signal transduction (CD44, DTR, DUSP6, EPS8, IGFBP3), DNA repair and transcription (FOXJ1), metabolic homeostasis (RASA1, SHMT2), cytoskeletal stability (MSN, MAPT) and cholesterol biosynthesis (FDFT1, FDPS).',NULL,NULL),
    ('XG','Xg blood group','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('TERT','telomerase reverse transcriptase','neurotrophic/neuroprotective','PMID:25632141;PMID:23968592;PMID:10854254','PMID:25632141;PMID:27974126',NULL,'In different cellular systems, TERT protein has been shown to be protective through its interaction with mitochondria. Our data reveal that TERT is expressed in vitro in mouse neurons and microglia, and in vivo in the cytoplasm of mature human hippocampal neurons and activated microglia, but is absent from astrocytes.;These data suggest that TERT plays a neuroprotective role via anti-apoptosis in neurons after OGD.;Our findings demonstrate a neuroprotective function of TERT in an experimental model  relevant  to  Alzheimer’s  disease, and  suggest  the  possibility  that  restoration  of  TERT expression  in  neurons  in  the  adult  brain  may  protect against  age-related  neurodegeneration.','Our data reveal that TERT is expressed in vitro in mouse neurons and microglia, and in vivo in the cytoplasm of mature human hippocampal neurons and activated microglia, but is absent from astrocytes.;TERT can inhibit cell apoptosis induced by HI and might have a neuroprotective role in developing brain with HIBD.',NULL),
    ('TES','testin LIM domain protein','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('CGA','glycoprotein hormones, alpha polypeptide','neurotrophic/neuroprotective',NULL,'10.5665/sleep.5148',NULL,NULL,'Our results indicate that TERT might function as an anti-apoptotic protein by inhibiting activation of caspase-3, while further studies are needed to evaluate underlying mechanisms.',NULL),
    ('DAP','death associated protein','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('PTH','parathyroid hormone','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('S100B','S100 calcium binding protein B','neurotrophic','PMID:22489319;PMID:15584905;PMID:17639288;PMID:26899964 ','PMID:20728493',NULL,'Microscopic examination of glia suggested signs of toxicity in cultures treated with 100 uM oxyresveratrol, as demonstrated by elevated S-100B protein release and a high proportion of cells with condensed nuclei.;Using a well-characterized in vitro model of brain cell trauma, we have previously shown that strain injury causes S100B release from neonatal rat neuronal plus glial cultures and that exogenous S100B reduces delayed post-traumatic neuronal damage even when given at 6 or 24 h post-trauma. The purpose of the current studies was to measure post-traumatic S100B release by specific brain cell types and to examine the effect of an antibody to S100 on post-traumatic delayed (48 h) neuronal injury and the protective effect of exogenous S100B.;Our data suggest that selective activation of CB1 receptors by either exogenous or endogenous cannabinoids might afford neuroprotection in MPTP-induced neurotoxicity also by controlling S100B up-regulation in activated glial cells.;Our results have shown that at nanomolar concentrations, S100b protects cells against AP. mediated cytotoxicity and the protective mechanism could be related, almost in part, to the control of ROS production through an over expression of Myoglobin gene.',' We measured BDNF and S100B protein levels in the serum, prefrontal cortex, striatum and hippocampus of rats in models of depression, i.e., olfactory bulbectomy (OBX) and chronic unpredictable stress (CUS) models.',NULL),
    ('FGF20','fibroblast growth factor 20','neurotrophic/neuroprotective','PMID:22971544',NULL,NULL,'Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson''s disease.',NULL,NULL),
    ('PSAP','prosaposin','neurotrophic','PMID:18481277',NULL,NULL,'Prosaposin is an AR-target gene and its neurotrophic domain upregulates AR expression and activity in prostate stromal cells.',NULL,NULL),
    ('PTN','pleiotrophin','neurotrophic/neuroprotective','PMID:27468976','PMID:22008908;PMID:27468976',NULL,'The data obtained indicate that the absence of PTN affects AKT pathway response and modulates the expression of genes related with neuroprotection (Mgst3 and Estrogen receptor 1, Ers 1) and cell differentiation (Caspase 6, Nestin, and Odz4), both in vivo and in vitro.','Striatal pleiotrophin overexpression provides functional and morphological neuroprotection in the 6-hydroxydopamine Model.;The data obtained indicate that the absence of PTN affects AKT pathway response and modulates the expression of genes related with neuroprotection.',NULL),
    ('HDGF','heparin binding growth factor','neurotrophic/neuroprotective',NULL,'PMID:22531700',NULL,NULL,'Quantitative retinal protein analysis after optic nerve transection reveals a neuroprotective role for hepatoma-derived growth factor on injured retinal ganglion cells.',NULL),
    ('CNP','2'',3''-cyclic nucleotide 3'' phosphodiesterase','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('HTT','huntingtin','neurotrophic/neuroprotective','11278258.0',NULL,'12062094;16452687','Here we report that Htt overexpression in other CNS-derived cells can protect them from more than 20 days exposure to fatal stimuli.[...] These data show that Htt inhibits neuronal cell death by interfering with the activity of the apoptosome complex.',NULL,'We demonstrate that huntingtin is a substrate of Akt and that phosphorylation of huntingtin by Akt is crucial to mediate the neuroprotective effects of IGF-1.;Using a rat model of HD based on lentiviral-mediated expression of a polyQ-huntingtin fragment in the striatum, we demonstrate here that phosphorylation of S421 is neuroprotective in vivo.'),
    ('GRIN2A','glutamate ionotropic receptor NMDA type subunit 2A','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('GRIN2B','glutamate ionotropic receptor NMDA type subunit 2B','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('TXN','thioredoxin','neurotrophic/neuroprotective','20298786;10.1074/jbc.M110701200;10.1093/abbs/37.2.119',NULL,'19940280.0','Electroretinography, immunocytochemistry, quantitative histology, RT-PCR and Western blots were used to obtain data which showed that thioredoxin overexpression prevented loss of photoreceptors and retinal function. Analysis of signal pathways showed that thioredoxin up-regulated neurotrophic factors BDNF and GDNF and activated survival signaling pathways Akt, Ras/Raf1/ and the ERKs while inhibiting the ASK1/JNK apoptosis pathway.;In this study, we showed that Trx in the submicromolar range protects neuronal SH-SY5Y cells from apoptosis caused by serum deprivation or by MPP+. Using antisense oligonucleotides and reductase inhibitors, we showed that preconditioning treatment of SH-SY5Y cells with a non-lethal serum-free stress produces a hormesis effect mediated by the induction of Trx and leads to enhanced tolerance against oxidative stress and apoptosis induced by either serum deprivation or by MPP+.; Trx mRNA transcription was inhibited by H2O2 (300 µM), which could be reversed by the pre-administration of DHEA in various concentrations (0.1–100 nM). Western blot assay confirmed that protein level of Trx could be elevated by the pre-treatment of DHEA (10–100 nM) with the exposure of H2O2. Taken together, these data suggest that DHEA may be useful in treating age-related neurodegenerative diseases based on its up-regulating effects on an antioxidant and neuroprotective protein thioredoxin, a substrate in the Trx redox system.',NULL,'Administration of female rats with 5,5-dithiobis-(2-nitrobenzoic acid) or [thioredoxin] small interfering RNA to the caudate nucleus decreased the protective effect of E(2) against FC-induced injury. [...] Increase of brain [thioredoxin] activity might play an important role in the E(2)-mediated neuroprotective effect against FC-induced brain injury in female rats.'),
    ('ENO2','enolase 2','neurotrophic/neuroprotective','10.1016/0168-0102(94)00849-B;22257123;23621429',NULL,NULL,'NSE promoted the survival of neurons not only in neocortical cultures but also in mesencephalic and spinal cord cultures. Furthermore, NSE showed neuroprotective action on cultured neocortical neurons in a low-oxygen atmosphere.;We show that gamma-enolase-mediated PI3K activation regulates RhoA kinase, a key regulator of actin cytoskeleton organization. Moreover, the inhibition of RhoA downstream effector ROCK (Rho-associated kinase) results in enhanced gamma-enolase-induced neurite outgrowth, accompanied by actin polymerization and its redistribution to growth cones. Our results show that gamma-enolase controls neuronal survival, differentiation and neurite regeneration by activating the PI3K/Akt and MAPK/ERK signalling pathways, resulting in downstream regulation of the molecular and cellular processes of cytoskeleton reorganization and cell remodelling, activation of transcriptional factors and regulation of the cell cycle.; The upregulation of c-enolase in microglial cells in response to amyloid-b peptide (Ab) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with gamma-enolase proved to be neuroprotective against Ab toxicity, however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of gamma-enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid-b-related neurodegeneration.',NULL,NULL),
    ('SEMA4D','semaphorin 4D','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('NRN1','neuritin 1','neurotrophic/neuroprotective','10.1038/cddis.2015.22;10.1038/cddis.2014.478;15606892;10.1007/s11064-018-2553-4','29334295.0',NULL,'The purpose of this study was to evaluate the neuroprotective and axogenic properties of Nrn1 on axotomized retinal ganglion cells (RGCs) in vitro and on the in vivo optic nerve crush (ONC) mouse model. Axotomized cultured RGCs treated with recombinant hNRN1 significantly increased survival of RGCs by 21% (n=6–7, P<0.01) and neurite outgrowth in RGCs by 141% compared to controls (n=15, P<0.05). RGC transduction with AAV2-CAG–hNRN1 prior to ONC promoted RGC survival (450%, n=3–7, P<0.05) and significantly preserved RGC function by 70% until 28 days post crush (dpc) (n=6, P<0.05) compared with the control AAV2-CAG–green fluorescent protein transduction group.;We also showed that soluble recombinant neuritin, when chronically infused into the brains of Tg2576 mice, normalized synaptic plasticity in acute hippocampal slices, leading to intact long-term potentiation. By revealing the protective actions of soluble neuritin against AD-related neural defects, we provide a potential therapeutic approach for patients with AD.;Finally, the androgenic effect on neurite outgrowth was abolished by silencing neuritin with siRNA. Therefore, the trophic effects of androgens in motor neurones may be explained by the androgenic regulation of neuritin, a protein linked to neurone development, elongation and regeneration.;GRP78, caspase-12 and CHOP expression as well as apoptosis rate of primary cultured neurons and the ultrastructural changes of endoplasmic reticulum in the OGD/R + neuritin group significantly improved compared with the OGD/R group. In conclusion, the neuroprotection function of neuritin may be involved in ERS pathways.','Our findings indicated that neuritin plays a protective role in TBI by improving neurological scores, repairing injured neurons and protecting the cortical neurons against apoptosis through inhibition of caspase-3 expression.',NULL),
    ('FLT3LG','fms related tyrosine kinase 3 ligand','neurotrophic',NULL,NULL,'10.1006/mcne.2001.1033',NULL,NULL,'FL synergized with NGF to promote the survival of cultured DRG neurons, although it lacked any neurotrophic activity alone. We conclude that FL serves as an adjunct trophic factor in the nervous system, which differs from its role in the hematopoietic system.'),
    ('GNRH1','gonadotropin releasing hormone 1','neurotrophic','10.15406/mojap.2016.02.00063',NULL,NULL,'GnRH was shown to induce changes in neurite outgrowth and length in rat cortical neurons in vitro.',NULL,NULL),
    ('NR4A2','nuclear receptor subfamily 4 group A member 2','neurotrophic/neuroprotective','PMID:28348207;27940361','PMID:28348207;PMID:27940361','PMID:26383113;PMID:26124091','In conclusion, Nurr1 overexpression exerts neuroprotective and anti-inflammatory roles via down-regulating CCL2 in both in vivo and in vitro PD models, contributing to developing mechanism-based and neuroprotective strategies against PD.;In the MPP(+)-pretreated PC12 cells, PPARgamma and Nurr1 agonists and their combined form resulted in a decrease in the cell death rate.','Here we report that Nuclear receptor-related 1 (Nurr1):Retinoid X receptor a (RXRa) activation has a double therapeutic potential for PD, offering both neuroprotective and symptomatic improvement. We designed BRF110, a unique in vivo active Nurr1:RXRa-selective lead molecule, which prevents DAergic neuron demise and striatal DAergic denervation in vivo against PD-causing toxins in a Nurr1-dependent manner.;Furthermore, Nurr1 overexpression remarkably relieved MPTP-induced movement disorder and spatial memory deficits and played neuroprotective and anti-inflammatory roles in MPTP-induced PD mice by down-regulating CCL2 in vivo.','C-DIM12 increased expression of transfected human Nurr1, induced Nurr1 protein expression in primary dopaminergic neurons and enhanced neuronal survival from exposure to 6-OHDA.;In particular, we found that two antimalarial drugs, amodiaquine and chloroquine stimulate the transcriptional function of Nurr1 through physical interaction with its ligand binding domain (LBD).'),
    ('PARK7','Parkinsonism associated deglycase','neurotrophic/neuroprotective','PMID:28165637','PMID:16860563;PMID:18003894 ','PMID:19276614;PMID:20087465;PMID:22041943;PMID:21372141 ','However, cells treated with exogenous extracellular DJ-1 during reperfusion exhibited significant rescue from OGD-induced cell death.','In this study, a recombinant DJ-1 protein was administrated into the brain of PD model rats that had been injected to 6-hydroxydopamine (6-OHDA) in the left substantia nigra. PD phenotypes, including dopaminergic neuron death in the substantia nigra, decrease in dopamine, and dopamine transporter levels in the striatum, and motor abnormality, were dramatically improved by wild-type DJ-1 but not L166P DJ-1, a mutant form of DJ-1 found in PD patients.;Importantly, DJ-1 expression decreases markers of oxidative stress after stroke insult in Vivo, suggesting that DJ-1 protects through alleviation of oxidative stress.','These results suggest that UCP0054278 interacts with endogenous DJ-1 and then exhibits antioxidant and neuroprotective responses.;These results suggest that UCP0045037 interacts with endogenous DJ-1 and produces a neuroprotective response.;These results suggest that UCP0054278 interacts with endogenous DJ-1 and then produces antioxidant and neuroprotective responses in both in vivo and in vitro models of PD.;After screening a number of small molecules, we have found that the histone deacetylase inhibitor phenylbutyrate increases DJ-1 expression by 300% in the N27 dopamine cell line and rescues cells from oxidative stress and mutant a-synuclein toxicity.'),
    ('HDAC7','histone deacetylase 7','neurotrophic',NULL,NULL,'PMID:30018556 ',NULL,NULL,'Among these compounds, 4j, 5c, and 5e displayed effective inhibitions for Aß self-aggregation, HDAC5 activity and HDAC7 activity with IC50 values of <10 uM.;'),
    ('UCP2','uncoupling protein 2','neurotrophic/neuroprotective','PMID:12960023','PMID:24965893;PMID:22266335;PMID:18018477','PMID:24670857;PMID:19356683 ','PC12 cells, when transfected with UCP2, were protected against free radical-induced cell death.','In primary DA neurons, rotenone-induced mitochondrial fragmentation and lethality is attenuated as the result of hucp2 expression.;Taken together, our results demonstrate a neuroprotective effect of hUCP2 in DA neurons in a Drosophila sporadic PD model.;The results showed that the expression of UCP2 and UCP5 was significantly elevated in the ischemic lesions compared to the intact area.','The protective effects of ghrelin after TBI and UH seem to be related to upregulation of UCP2 expression in the brain and requiring the intact vagus nerve;In the present study, we tested two hypotheses: (a) that neuroprotection against cerebral ischemia can be induced by RPC in vivo, and (b) that RPC neuroprotection involves alterations in mitochondrial function via the SIRT1 target mitochondrial uncoupling protein 2 (UCP2). [...] In conclusion, in vivo resveratrol pretreatment confers neuroprotection similar to IPC via the SIRT1-UCP2 pathway.'),
    ('CBL','Cbl proto-oncogene','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('MIA','melanoma inhibitory activity','no trophic/protective activity identified',NULL,' ',' ',' ',' ',' '),
    ('TH','tyrosine hydroxylase','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('THOP1','thimet oligopeptidase 1','neurotrophic/neuroprotective','PMID:18571100',NULL,NULL,'Functional modulation of THOP1 levels in primary cortical neurons demonstrated that its overexpression was neuroprotective against Abeta toxicity',NULL,NULL),
    ('CRLF3','cytokine receptor like factor 3','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('ATF3','activating transcription factor 3','no trophic/protective activity identified','PMID:18194435',NULL,NULL,'Forced inhibition of ATF-3 expression using siRNA protects neurons against LK-induced apoptosis, whereas the over-expression of ATF-3 blocks GW5074-mediated neuroprotection.',NULL,NULL),
    ('HDAC4','histone deacetylase 4','neurotrophic','PMID:23480850;PMID:23349832','PMID:27660204',NULL,'We further found that both HDAC4 and HDAC5 increased cell viability through inhibition of HMGB1, a central mediator of tissue damage following acute injury, expression and release in PC12 cells.;We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington''s disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington''s and Alzheimer''s disease brains.','These findings indicate that HDAC4 regulates thimerosal-induced cell death in neurons and that treatment with MC1568 prevents thimerosal-induced activation of caspase-3 in the rat PFC.',NULL),
    ('NPY','neuropeptide Y','neurotrophic/neuroprotective','PMID:26311075;PMID:23358924;PMID:18412629;PMID:17212973','22537092;PMID:21816512;PMID:19318226;PMID:19176820 ',NULL,'Using in vitro cultures of rat retinal explants exposed to NMDA, we found that NPY pretreatment prevented NMDA-induced cell death.;Using in vitro models of Alzheimer''s disease (AD), we found that the toxic effects of amyloid beta 25-35 (Aß(25-35)) on the neurotrophin brain-derived neurotrophic factor (BDNF) were counteracted by pre-incubation with neuropeptide Y (NPY), a neuropeptide expressed within the central nervous system.;Thus, an increase of AMPA-receptor mediated neurodegeneration, in the mouse hippocampus, was prevented by neuroprotective pathways activated by NPY receptors (Y(1) and Y(2)), which can be affected by BDNF released by microglia and neurons.;The activation of Y(1) or Y(2) receptors 30min after starting the exposure to the excitotoxic insult with kainate resulted in neuroprotection by reducing the PI uptake in DG, CA1 and CA3 cell layers.','Our data indicate that intracerebroventricular administration of exogenous NPY (at the dose of 2 ug/2 uL, 4 days after TMT-administration), in adult rats, exerts a protective role in regard to TMT-induced hippocampal damage and a proliferative effect on the hippocampal neurogenic niche through the up-regulation of Bcl-2, Bcl2l1, Bdnf, Sox-2, NeuroD1, Noggin and Doublecortin genes, contributing to delineate more clearly the role of NPY in in vivo neurodegenerative processes.;In rat and mice models of PD, striatal injection of NPY preserved the nigrostriatal dopamine pathway from degeneration as evidenced by quantification of (1) tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta, levels of (2) striatal tyrosine hydroxylase and dopamine transporter, (3) dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) as well as (4) rotational behavior.;The obtained results indicate that neuropeptide Y produces neuroprotective effect via Y2 and Y5 receptors, and that the compounds may be effective after delayed application.;Infusion of these NPY CTFs into the brains of APP (amyloid precursor protein) tg mice ameliorated the neurodegenerative pathology in this model. Moreover, the amidated NPY CTFs protected human neuronal cultures from the neurotoxic effects of Abeta.',NULL),
    ('GPNMB','glycoprotein nmb','neurotrophic/neuroprotective','PMID:22891158;PMID:29519253 ','PMID:25010402',NULL,'In an NSC34 cell line, glycosylation of GPNMB was inhibited by interaction with SOD1(G93A), increasing motor neuron vulnerability, whereas extracellular fragments of GPNMB secreted from activated astrocytes attenuated the neurotoxicity of SOD1(G93A) in neural cells.;These results demonstrate that GPNMB may exert its neuroprotective effect through reducing astrocyte-mediated neuroinflammation in a CD44-dependent manner, providing novel mechanistic insight into the neuroprotective properties of GPNMB.','These results indicate that GPNMB protected neurons against IRI, and phosphor-Akt and phosphor-ERK might be a part of the protective mechanisms, and that the neuroprotective effect of GPNMB was seemingly induced by the extracellular sequence of GPNMB.',NULL),
    ('SIRT3','sirtuin 3','neurotrophic/neuroprotective','PMID:23139766;PMID:25452082;PMID:29567426;PMID:28197079 ','PMID:26058697;PMID:26698917 ',NULL,'Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective.;Moreover, treatment with IC87201 and ZL006 significantly increased the expression of Sirt3 after MPP(+) exposure, and knockdown of Sirt3 using specific targeted small interfere RNA (siRNA) partially nullified the protective effects induced by these two inhibitors.;In conclusion, miR-494-3p inhibition exerted a neuroprotective role in MPP+-induced PD by targeting SIRT3, providing a possible therapeutic strategy for PD patients.;Furthermore, SIRT3 knockdown in NSCs via small interfering RNA (siRNA) accelerated cell injury, whereas SIRT3 overexpression provided resistance to microglia activation-induced oxidative stress cellular damage.','We further showed that ketones'' effects were achieved by upregulating NAD(+)-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones'' beneficial effects.;Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress. AAV-mediated Sirt3 gene delivery restores neuronal stress resistance.',NULL),
    ('SOCS1','suppressor of cytokine signaling 1','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('GDF15','growth differentiation factor 15','neurotrophic/neuroprotective',NULL,'PMID:11102463',NULL,NULL,'Unilateral injections of GDF-15/MIC-1 into the medial forebrain bundle just above the substantia nigra (SN) and into the left ventricle (20 microgram each) immediately before a 6-OHDA injection (8 microgram) prevented 6-OHDA-induced rotational behavior and significantly reduced losses of DAergic neurons in the SN. This protection was evident for at least 1 month.',NULL),
    ('LIF','leukaemia inhibitory factor','neurotrophic/neuroprotective','PMID:9189906',NULL,NULL,'Early postnatal spiral ganglion cells (SGC) in a dissociated cell culture were used as a model of auditory innervation to test the trophic factors leukaemia inhibitory factor (LIF) and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings suggest that LIF supports neuronal survival in a concentration-dependent manner.',NULL,NULL),
    ('CTF1','Cardiotrophin 1','neurotrophic/neuroprotective',NULL,'PMID:17178916',NULL,NULL,'Here we show that administration of CT-1 to rats or mice protects against I/R liver injury and that CT-1-deficient mice are exceedingly sensitive to this type of damage.',NULL),
    ('OSM','oncostatin M','neurotrophic/neuroprotective','PMID:17023520;PMID:24996996','PMID:26311783;PMID:17023520;PMID:24996996',NULL,'Using primary cultures of mouse cortical neurons, OsM was shown to reduce N-methyl-D-aspartate (NMDA) -induced neuronal death by 50% when added simultaneously with NMDA while pretreatment of neurons with OsM fully prevented NMDA toxicity indicating a profound protective effect of this cytokine. OsM was also shown to inhibit NMDA-mediated increase in levels of free intracellular calcium and to selectively reduce neuronal expression of the NR2C subunit of the NMDA receptor.;Furthermore, OSM dose-dependently promoted neurite outgrowth in cultured neurons, indicating that the cytokine plays an additional role in CNS repair.','Using gain- and loss-of-function approaches, we demonstrated that decreased neuronal OSMR expression results in deteriorated stroke outcomes but that OSMR overexpression in neurons is cerebroprotective. Moreover, administering recombinant human OSM to mice before the onset of I/R showed that human OSM can be protective in rodent models of ischemic stroke.;Finally, using an in vivo model of excitotoxic injury, OsM significantly reduced the NMDA-induced lesion volume when coinjected with NMDA into the mouse striatum.;Indeed, our in vivo experiments demonstrate that OSM treatment increases plasticity of serotonergic fibers after SCI. Together, our data show that OSM is produced at the lesion site, where it protects the CNS from further damage and promotes recovery.',NULL),
    ('NRG1','neuregulin 1','neurotrophic/neuroprotective','PMID:18410912;PMID:22186019',NULL,NULL,'When B35 neurons were subjected to oxygen glucose deprivation (OGD)/reoxygenation or glutamate, widespread neuronal death was seen after both treatments. Treatment with NRG-1 immediately after OGD significantly increased neuronal survival.;Moreover, NRG1 reduced the number of Swe-APP- and Aß(1-42)-induced TUNEL-positive SH-SY5Y cells and primary cortical neurons, respectively. NRG1 reduced the accumulation of reactive oxygen species and attenuated Swe-APP-induced mitochondrial membrane potential loss.',NULL,NULL),
    ('BMP7','Bone Morphogenetic Protein 7','neurotrophic/neuroprotective','PMID:19765637;PMID:22461901',NULL,'PMID:15126117','Here, we show that BMP7 treatment of rats subjected to mild cervical SCI significantly increased the pro-survival mitogen-activated protein kinase-38 (MAPK-38) pathway and levels of N-methyl-D-aspartate receptor 1 (NMDAR-1) resulting in a significant increase in neuronal sparing in the ventral horn of the spinal cord. Moreover, BMP7 was neuroprotective against glutamate-mediated excitotoxicity in cultured cortical neurons.;Subsequent in vitro analyses of E14.5 cortical cells revealed that lack of Bmp7 affects neural progenitor cells, evidenced by their reduced proliferation, survival and self-renewal capacity. Addition of BMP7 was able to rescue these proliferation and survival defects.',NULL,'BMP7-induced protection was antagonized by the p42,44 MAPK kinase inhibitors PD98059 and U0125. The p38 MAPK antagonist SB203580, and their inactive analog SB202474, also attenuated BMP7-induced protection, suggesting that the interaction with p38 MAPK is nonspecific.'),
    ('IGF2','insulin like growth factor 2','neurotrophic/neuroprotective','PMID:28575743;PMID:23497056',NULL,NULL,'We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). [...] IGF-II was also able to recover the long-lasting neuronal cell damage.;IGF1 receptor (IGF1R) immunoreactivity was predominantly expressed by neurons, and both IGF1 and IGF2 significantly protected neurons from cytokine (IL-1/IFNa) induced death.',NULL,NULL),
    ('LEP','leptin','neurotrophic/neuroprotective','10.1093/cercor/bhw272','10.1038/cddis.2011.125',NULL,'Here we show that the leptin (116–130) fragment, but not leptin (22–56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116–130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116–130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity.','Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia.',NULL),
    ('BMP2','Bone Morphogenetic Protein 2','neurotrophic/neuroprotective','PMID:24686133',NULL,NULL,'In this study, we found that BMP2 exerts neurotrophic effects, including a neuroprotective effect against nocodazole-induced neuritic degeneration, on neuronal cells. We also found that BMP2-induced neurotrophic effects are directly involved in Smad-dependent signaling as well as PI3K/PTEN-Akt-mTOR signaling.',NULL,NULL),
    ('BMP4','Bone Morphogenetic Protein 4','neurotrophic/neuroprotective','PMID:15555930;10.1111/jnc.14281',NULL,NULL,'CNTF and BMP4, but not NGF or BDNF, greatly reduced the number of cells destroyed by toxin treatment indicating that these factors protect retinal neurons from a severe excitotoxic insult.;Interestingly, pharmacological inhibition of the ALK2 receptor prevented neuroprotection by STI1, while activation of ALK2 receptors by bone morphogenetic protein 4 (BMP4) either before or after OGD was effective in decreasing neuronal death induced by ischemia.',NULL,NULL),
    ('STIP1','Stress Induced Phosphoprotein 1','neurotrophic/neuroprotective',NULL,NULL,'10.1111/jnc.14281',NULL,NULL,'Our results demonstrated that STI1 treatment significantly decreased apoptosis and cell death in mouse neurons submitted to OGD in a manner that was dependent on PrPC and a7nAChR, but also on the activin A receptor 1 (ALK2), which has emerged as a signaling partner of STI1.'),
    ('BMP6','Bone Morphogenetic Protein 6','neurotrophic/neuroprotective','PMID:11546913;PMID:24903778;PMID:17628512','PMID:11546913',NULL,'Application of H(2)O(2) increased lactate dehydrogenase activity and decreased the density of MAP-2(+) neurons in culture. Both responses were attenuated by BMP6 pretreatment.;Our data demonstrated that BMP6 prevented apoptosis induced by a high dose of Aß25-35, and inhibited rod formation induced by low dose of Aß25-35 in hippocampal neurons.;We demonstrate that presence of BMP6 either before or after H(2)O(2)-induced injury protects the cultured primary cortical cells from apoptosis.','Complementary in vivo studies showed that pretreatment with BMP6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats.',NULL),
    ('CSF1','Colony Stimulating Factor 3','neurotrophic/neuroprotective',NULL,'PMID:18602391;PMID:25468272',NULL,NULL,'2 weeks after the insult, the RGC densities in the central and mid-peripheral retinas in ON-crushed, G-CSF-treated rats were significantly higher than that of the corresponding ON-crushed, PBS-treated rats (survival rate was 60% vs. 19.6% in the central retina, 46.5% vs. 23.9% in mid-peripheral retina, respectively, p<0.001). FVEP measurements showed a significantly better preserved latency of the p1 wave in the ON-crushed, G-CSF-treated rats than the ON-crushed, PBS-treated rats (78+/-9 ms in the sham operation group, 98+/-16 ms in the G-CSF-treated group, and 174+/-16 ms in the PBS-treated group, p<0.001).;In mice subjected to controlled cortical impact (CCI) we show that treatment with granulocyte macrophage colony stimulating factor (GM-CSF) affects regulatory T cell numbers coincident with decreased lesion volumes and increased cortical tissue sparing. This paralleled increases in neurofilament and diminished reactive microglial staining.',NULL),
    ('SNX1','Sorting Nexin 1','neurotrophic','10.1111/jnc.12524 ',NULL,NULL,'In Neuro-2a neuroblastoma cells, expression of either EFA6A or SNX1 induced neurite outgrowth, which was further enhanced by co-expression of EFA6A and SNX1.',NULL,NULL),
    ('PSD','Pleckstrin And Sec7 Domain Containing','neurotrophic','10.1111/jnc.12524 ',NULL,NULL,'In Neuro-2a neuroblastoma cells, expression of either EFA6A [PSD] or SNX1 induced neurite outgrowth, which was further enhanced by co-expression of EFA6A and SNX1.',NULL,NULL),
    ('SERPINF1','Serpin Family F Member 1','neurotrophic/neuroprotective','PMID:19442875',NULL,NULL,'The neurotoxic effect of rotenone (25nM) on dopaminergic neurons is reversed by addition of PEDF. [..] PEDF (1ng/ml) has also a neuroprotective effect in the 6-OHDA midbrain in vitro model.',NULL,NULL),
    ('NTRK2','neurotrophic receptor tyrosine kinase 2','neurotrophic','10.1038/celldisc.2016.30',NULL,NULL,'We found that activation of NTRK2 is able to confer a full growth phenotype of Ba/F3 cells in an IL3-independent manner in the PTEN-null setting.',NULL,NULL),
    ('CNTF','Ciliary Neurotrophic Factor','neurotrophic/neuroprotective','PMID:15555930','PMID:25896245',NULL,'CNTF and BMP4, but not NGF or BDNF, greatly reduced the number of cells destroyed by toxin treatment indicating that these factors protect retinal neurons from a severe excitotoxic insult.','Employing a murine model of retinal disease, we demonstrate that ciliary neurotrophic factor (CNTF) confers life-long protection against photoreceptor degeneration. Repetitive retinal imaging allowed the survival of intrinsically fluorescent cone photoreceptors to be quantified in vivo.',NULL),
    ('FGF2','fibroblast growth factor 2','neurotrophic/neuroprotective','PMID:16326808;PMID:19782732;PMID:10996460;PMID:9469637;PMID:9202296','10.1155/2017/2923182;PMID:26642808;PMID:17064673',NULL,'FGF-2 increased the number of proliferating cells in the subventricular zone by 30% in wild-type mice, and by 150% in HD transgenic R6/2 mice. [...] FGF-2 was neuroprotective as well, because it blocked cell death induced by mutant expanded Htt in primary striatal cultures.;Thus, our results demonstrate for the first time that the FGF2/ATP complex but not FGF2 alone mediates neuroprotection.;In  addition, co-culture of dopaminergic neurons with high molecular weight fibroblast growth factor-2 over-expressing Schwann cells revealed an increased survival and neurite formation of the mesencephalic dopaminergic neurons. These results suggest that the high molecular weight fibroblast growth factor-2 isoforms may serve as a new tool for the treatment of Parkinson''s disease.;These data strongly suggest that bFGF and BDNF promote the formation of neuronal circuits as well as survival and that optical recording of organotypic hippocampal slices would be a useful technique that enables us to analyze neuronal circuit formation easily.;Our study shows that stimulation of glial cells by bFGF allows the up-regulation of antioxidant defenses and supports cell survival during oxidative stress.','Our results indicated that pretreatment of FGF2 played a neuroprotective role in the early stage of rat mild TBI through alleviating brain edema, reducing neurological deficits, preventing tissue loss, and increasing the number of surviving neurons in injured cortex and the ipsilateral hippocampus.;Here, we demonstrate that lack of FGF-2 results in an increased volume of the striatal target area in mice.;These findings point to differences in the response of aged versus young adult rats to  FGF-2 in cerebral ischemia, and suggest that such differences need to be considered in the development of neuroprotective agents for stroke.',NULL),
    ('FGF19','fibroblast growth factor 19','neurotrophic/neuroprotective','10.1167/iovs.07-1272;PMID:18385093',NULL,NULL,'The addition of FGF-19 to Y79 retinoblastoma or primary adult pig photoreceptor cultures led to time- and dose-dependent changes in proliferation (for Y79) or survival (for primary photoreceptors). [...] The addition of FGF-19 led to the reexpression of Nrl immunoreactivity in both culture models.;These data indicate a physiological role for FGF-19 in adult photoreceptor phenotypic maintenance and survival and argue in favor of its use as a neuroprotectant.',NULL,NULL),
    ('FGF8','fibroblast growth factor 8','neurotrophic/neuroprotective','PMID:10350562;10.1001/archneur.65.6.753;10.1016/S0006-8993(01)02726-3;PMID:25259688',NULL,NULL,'We report here that another FGF family member, FGF-8 is able to protect rat hippocampal cultures from oxidative stress. The b isoform of FGF-8 protected hippocampal cultures from hydrogen peroxide with an EC50 of approximately 25 ng/ml.;Mesenchymal stromal cells were cultivated for 2 to 3 passages and neural differentiation was induced with fibroblast growth factor 2, fibroblast growth factor 8, and brain-derived neurotrophic factor.;Functionally, FGF8 promoted neurite outgrowth in human neuroblastoma SK-N-MC cells as well as in rat pheochromocytoma PC12 cells, suggesting that FGF8 acts as a neurotrophic factor. FGF8 also supported neuronal survival and differentiation in cultured human neural progenitor cells.;The results showed that both migration and proliferation was induced by FGF8.',NULL,NULL),
    ('FGF21','fibroblast growth factor 21','neurotrophic/neuroprotective','PMID:24468826',NULL,NULL,'Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition.',NULL,NULL),
    ('FGF13','fibroblast growth factor 13','neurotrophic','PMID:28922963',NULL,NULL,'Administration of FGF13 not only promoted neuronal polarization, axon formation, and growth cone initiation in vitro, but it also facilitated functional recovery following SCI. In addition, we found that upregulation of FGF13 in primary cortical neurons was accompanied by enhanced mitochondrial function, which is essential for axon regeneration.',NULL,NULL),
    ('TGFB1','Transforming growth factor-beta 1','neurotrophic/neuroprotective','PMID:14526228;PMID:14514014','PMID:19327151',NULL,'An adenovirus expressing a constitutively active form of TGF-beta 1 was injected intracerebrally 1 week before the induction of excitotoxic lesion, and neuronal protection was observed. To confirm the neuroprotective role of TGF-beta 1, the TGF-beta 1 adenovirus was replaced by recombinant human TGF-beta 1 protein and total neuroprotection was observed.;In vitro, TGF-beta1 protects neurons against excitotoxicity by inhibiting the t-PA-potentiated NMDA-induced neuronal death through a mechanism involving the up-regulation of the type-1 plasminogen activator inhibitor (PAI-1) in astrocyte','By using a well established neuropathic pain animal model (partial ligation of the sciatic nerve), we demonstrated that intrathecal infusion of recombinant TGF-ß1 significantly attenuated nerve injury-induced neuropathic pain.',NULL),
    ('KL','Klotho','neurotrophic/neuroprotective','PMID:25037225;10.1111/jnc.13902',NULL,NULL,'Pretreatment of rat primary hippocampal neurons and mouse hippocampal neuronal cell line HT22 with recombinant Klotho protected these cells from glutamate and oligomeric amyloid ß (oAß)-induced cytotoxicity. In addition, primary hippocampal neurons obtained from Klotho-overexpressing mouse embryos were more resistant to both cytotoxic insults, glutamate and oAß, compared with neurons from wild-type littermates.;Here, we show that klotho is a key factor underlying the neuroprotective effect of latanoprost during post-axotomy retinal ganglion cell (RGC) degeneration.',NULL,NULL),
    ('ZNF346','Zinc Finger Protein 346','neurotrophic/neuroprotective','10.1074/jbc.M114.597575',NULL,NULL,'We found that JAZ protects cerebellar granule neurons against potassium deprivation-induced death and cortical neurons from death resulting from oxidative stress. JAZ also protects neurons against toxicity induced by mutant huntingtin and mutant ataxin-1 expression.',NULL,NULL),
    ('CHL1','Cell Adhesion Molecule L1 Like','neurotrophic','PMID:15880726',NULL,NULL,'CHL1-Fc saved the same number of motoneurons as did L1-Fc, whereas P0-Fc had little neurotrophic activity at the same concentrations. Survival induced by L1 and CHL1 was completely inhibited by 20 microM LY294002 and PD98059, indicating that both MEK and PI3K pathways are required for signaling by these molecules.',NULL,NULL),
    ('L1CAM','L1 Cell Adhesion Molecule','neurotrophic','PMID:15880726',NULL,NULL,'L1-Fc prevented the death of approximately half of the motoneurons that were saved by BDNF in a dose-dependent manner (EC50 = 10 pM). CHL1-Fc saved the same number of motoneurons as did L1-Fc, whereas P0-Fc had little neurotrophic activity at the same concentrations.',NULL,NULL),
    ('SSPO','SCO-Spondin','neurotrophic/neuroprotective','PMID:24667843','PMID:24667843',NULL,'SCO-spondin stimulates neuronal differentiation and neurite growth in vitro. [...] The objective of this work was to assess the neuroprotective and neuroregenerative properties of NX210 in vitro and in vivo for the treatment of spinal cord injury (SCI). In vitro studies were carried out on the B104 neuroblastoma cell line demonstrating neuroprotection by the resistance to oxidative damage using hydrogen peroxide and the measure of cell viability by metabolic activity.','In vivo studies were performed in two rat models of SCI: (1) a model of aspiration of dorsal funiculi followed by the insertion of a collagen tube in situ to limit collateral sprouting, white matter regeneration was assessed using neurofilament immunostaining, (2) a rat spinal cord contusion model to assess functional recovery using BBB scale and reflex testing. We demonstrate for the first time that NX210 (a) provides neuroprotection to oxidative stress in the B104 neuroblastoma cells, (b) stimulates axonal regrowth in longitudinally oriented neofibers in the aspiration model of SCI and (c) significantly improves functional recovery in the contusive model of SCI.',NULL),
    ('TIMP2','TIMP metallopeptidase inhibitor 2','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('TIMP4','TIMP metallopeptidase inhibitor 4','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('EPO','erythropoietin','neurotrophic/neuroprotective','PMID:28849166;PMID:30062636;PMID:26357589;PMID:25585642',NULL,NULL,'Our data suggests that moderate elevated brain Epo levels provide clinically significant neuroprotection in EAE without modulation of the immune response making a significant contribution.;The synergistic combination dose down regulated neuroinflammatory genes (Tnf-a, Il1b, Nf-kB, and iNos) and upregulated the neuroprotective genes (Bcl-2, Bcl-xl, Hif-1, and Epo).;The established EPO-overexpressing NIH/3T3 cell line, EPO-3T3-EGFP, may provide a material for future studies of cell-based therapies for neurodegenerative diseases via the secretion of EPO on a short-term, high-dose, regional basis.;These results imply that EPO might be a novel valuable agent for treating AGEs-induced Toxicity.',' ',NULL),
    ('TNFRSF1A','TNF receptor superfamily member 1A','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('TNFRSF18','TNF receptor superfamily member 18','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('TNFRSF1B','TNF receptor superfamily member 1B','no trophic/protective activity identified',NULL,NULL,NULL,NULL,NULL,NULL),
    ('BOK','BOK, BCL2 family apoptosis regulator','neurotrophic/neuroprotective','PMID:27098698','PMID:27098698',NULL,'We show that Bok controls neuronal Ca(2+)homeostasis and bioenergetics and, contrary to previous assumptions, exerts neuroprotective activities in vitro and in vivo.','We show that Bok controls neuronal Ca(2+)homeostasis and bioenergetics and, contrary to previous assumptions, exerts neuroprotective activities in vitro and in vivo.',NULL),
    ('MTOR','mechanistic target of rapamycin kinase','neurotrophic/neuroprotective',NULL,NULL,NULL,NULL,NULL,NULL),
    ('ARG1','arginase 1','neurotrophic/neuroprotective',NULL,'PMID:24655927',NULL,NULL,'The results show that Arg1 and iNOS, thought to have opposing inflammatory properties, are upregulated in microglia during disease progression and that Arg1  in motor neurons may confer protection from disease processes. Further understanding of the neuroinflammatory response, and the Arg1/iNOS balance in motor neurons, may provide suitable therapeutic targets for ALS.',NULL),
    ('GBA','glucosylceramidase beta','neurotrophic/neuroprotective',NULL,'PMID:26392287',NULL,NULL,'In rats, co-injection of AAV-GBA1 with AAV-A53T a-synuclein into the substantia nigra prevented a-synuclein-mediated degeneration of nigrostriatal dopamine neurons by 6 months. These neuroprotective effects were associated with altered protein expression of markers of autophagy.',NULL),
    ('GAL','galanin and GMAP prepropeptide','neurotrophic/neuroprotective','PMID:26764217','PMID:28203483;PMID:26764217;PMID:24726665',NULL,'Our results indicate the potential therapeutic value of agonists selective for GAL1R in the prevention of neuronal cell death.','These results suggested that exogenous GAL protects the brain from ischemic injury by inhibiting Capsase-8/12-initiated apoptosis, possibly mediated by GalR1 via the cPKCa signaling pathway.;Our results indicate the potential therapeutic value of agonists selective for GAL1R in the prevention of neuronal cell death.;Our findings establish the role of galanin as a modulator of neural stem cell function and support the importance of galanin for brain plasticity and repair.',NULL),
    ('VIP','vasoactive intestinal peptide','neurotrophic/neuroprotective','PMID:25712659',NULL,NULL,'The obtained results showed that hypoxia/ischemia may trigger down-regulation of the brain AC-coupled PACAP/VIP receptors, with a consequent decrease of PACAP- and/or VIP-ergic-dependent cAMP-driven signaling. Moreover, our findings indicate that PACAP and VIP can prevent the deleterious effect of OGD on rat neuronal cells.',NULL,NULL);
