Role of alpha-synuclein phosphorylation at Serine 129 in methamphetamine-induced neurotoxicityin vitroandin vivo
Role of alpha-synuclein phosphorylation at Serine 129 in methamphetamine-induced neurotoxicityin vitroandin vivo
复制标题
α-突触核蛋白丝氨酸 129 磷酸化在甲基苯丙胺诱导的体外和体内神经毒性中的作用
DOI：
10.1097/wnr.0000000000001495
复制
发表时间：
2020-08-05
期刊：
影响因子：
1.7
通讯作者：
Qiu, Pingming
中科院分区：
文献类型：
--
作者：
Ding, Jiuyang;Wang, Yue;Qiu, Pingming
α-突触核蛋白（α-Syn）的磷酸化和聚集在甲基苯丙胺（METH）诱导的多巴胺能神经毒性中起关键作用。甲基苯丙胺诱导的神经毒性和α-Syn之间相互作用的确切机制尚不清楚。我们的目的是在体外和体内研究α-Syn的丝氨酸129磷酸化（pS129）在其聚集和神经毒性中的作用。在本研究中，我们在蛋白磷酸化和基因水平上检测了pS129 α-Syn在体外和体内的表达，并评估了其对MET诱导的神经毒性的影响。在此，我们发现METH处理后pS129 α-Syn显著增加;此外，抑制α-Syn磷酸化后，METH暴露引起的神经元α-Syn聚集和凋亡显著减弱。我们证明pS129 α-Syn有助于α-Syn的聚集，并且磷酸化和聚集形式的α-Syn在多巴胺能神经元和SH-SY 5 Y细胞中的MET诱导的神经毒性中起重要作用，支持对MET诱导的神经毒性的治疗的潜在见解。
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.