Alpha-lipoic acid alleviated 6-OHDA-induced cell damage by inhibiting AMPK/mTOR mediated autophagy

Abstract

Oxidative stress and autophagy are involved in the pathogenesis of Parkinson's disease. The relationship between oxidative stress and autophagy is a hot spot of scientific research. Alpha-lipoic acid (ALA) is a natural antioxidant. ALA has been reported to reduce oxidative stress and apoptosis in PD models, but its role in autophagy regulation of PD has been reported very little. In this study, we investigated the protective effects of ALA on 6-OHDA induced neurotoxicity, and explored the potential mechanisms associated with the crosstalk between oxidative stress and autophagy. Our results showed that 6-OHDA induced accumulation of ROS in SH-SY5Y cells, accompanied by excessive autophagy and apoptosis. ALA protected against 6-OHDA induced neuronal death through inhibition of oxidative stress and autophagy. Furthermore, we found that ALA inhibited AMPK phosphorylation while activated mTOR phosphorylation thereby blocking AMPK/mTOR signaling pathway involved autophagy. In conclusion, ALA alleviated 6-OHDA induced cell injury possibly by inhibiting autophagy mediated by AMPK/mTOR pathway.