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.