Alpha-lipoic acid alleviated 6-OHDA-induced cell damage by inhibiting AMPK/mTOR mediated autophagy
Alpha-lipoic acid alleviated 6-OHDA-induced cell damage by inhibiting AMPK/mTOR mediated autophagy
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DOI：
10.1016/j.neuropharm.2019.04.009
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发表时间：
2019-09
影响因子：
4.7
通讯作者：
Lina Zhou;Yan Cheng
中科院分区：
文献类型：
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作者：
Lina Zhou;Yan Cheng
氧化应激和自噬参与帕金森病的发病机制。氧化应激与细胞自噬的关系一直是科学研究的热点。α-硫辛酸（ALA）是一种天然抗氧化剂。ALA在PD模型中具有降低氧化应激和细胞凋亡的作用，但其在PD自噬调控中的作用报道甚少。本研究探讨了ALA对6-OHDA诱导的神经毒性的保护作用，并探讨了氧化应激与自噬相互作用的可能机制。我们的研究结果表明，6-OHDA诱导SH-SY 5 Y细胞ROS的积累，伴随着过度的自噬和凋亡。ALA通过抑制氧化应激和自噬保护6-OHDA诱导的神经元死亡。此外，我们发现ALA抑制AMPK磷酸化，同时激活mTOR磷酸化，从而阻断AMPK/mTOR信号通路参与自噬。结论：ALA可能通过抑制AMPK/mTOR通路介导的自噬而减轻6-OHDA诱导的细胞损伤。
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.