The phosphorylation and aggregation of alpha-synuclein (alpha-Syn) play a key role in methamphetamine (METH)-induced dopaminergic neurotoxicity. The exact mechanism underlying the interaction between METH-induced neurotoxicity and alpha-Syn was poorly clarified. We aimed to figure out the role of serine 129 phosphorylation (pS129) of alpha-Syn on its aggregation and neurotoxicityin vitroandin vivo. In this study, we examined pS129 alpha-Syn expressionin vitroandin vivoat the protein phosphorylation and genetic levels and evaluated its effect on METH-induced neurotoxicity. Here, we found that pS129 alpha-Syn was significantly increased after METH treatment; moreover, the neuronal alpha-Syn aggregation and apoptosis caused by METH exposure were significantly attenuated after inhibiting alpha-Syn phosphorylation. We demonstrate that pS129 alpha-Syn contributes to the aggregation of alpha-Syn, and that phosphorylated and aggregated forms of alpha-Syn play an important role in METH-induced neurotoxicity in dopaminergic neurons and SH-SY5Y cells, supporting a potential insight into the treatment of METH-induced neurotoxicity.
[1]Southern Med Univ, Sch Forens Med, Guangzhou 510515, Guangdong, Peoples R China.
[2]Kingmed Inst Forens Sci, Guangzhou, Guangdong, Peoples R China.
[3]Kunming Med Univ, Sch Forens Med, Kunming, Yunnan, Peoples R China.
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