miR-494-3p modulates the progression of in vitro and in vivo Parkinson's disease models by targeting SIRT3

Parkinson's disease (PD) is the second most prevalent chronic and progressive neurodegenerative disease. Plenty of miRNAs have been demonstrated to participate in the pathogenesis of PD. However, the detailed roles of miR-494-3p and underlying mechanisms involved in PD progression remain to be explored. In the present study, we found that miR-494-3p expression was increased and sirtuin 3 (SIRT3) expression was decreased in SH-SY5Y cells following l-Methyl-4-phenylpyridinium (MPP (+) ) treatment. Loss-of-function showed that miR-494-3p inhibition promoted cell viability and superoxide dismutase (SOD) activity, and suppressed apoptotic rate, caspase-3 activity, lactate dehydrogenase (LDH) activity, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) expressions, and reactive oxygen species (ROS) generation in MPP+-induced SH-SY5Y cells. Moreover, SIRT3 was identified as a target of miR-494-3p and miR-494-3p negatively regulated SIRT3 expression in SHSY5Y cells. Additionally, up-regulation of miR-494-3p suppressed SIRT3 expression and exacerbated motor impairment in l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. 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.