The effect of α-synuclein and Tau in methamphetamine induced neurotoxicity in vivo and in vitro
The effect of α-synuclein and Tau in methamphetamine induced neurotoxicity in vivo and in vitro
复制标题
α-突触核蛋白和 Tau 在甲基苯丙胺诱导的体内和体外神经毒性中的作用
DOI：
10.1016/j.toxlet.2019.11.028
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发表时间：
2020-02-01
影响因子：
3.5
通讯作者：
Qiu, Pingming
中科院分区：
文献类型：
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作者：
Ding, Jiuyang;Lian, Yongling;Qiu, Pingming
上调的α-突触核蛋白（α-syn）和Tau共同出现在甲基苯丙胺（METH）滥用者的大脑中。在这里，我们设计的实验主要是为了研究在METH暴露中α-syn和Tau是否相互作用。我们在体外和体内条件下检测了METH暴露后α-syn、总Tau的表达和Tau在丝氨酸396处的磷酸化（pSer 396 Tau），以确定α-syn和Tau的共同出现。我们还通过在METH处理中沉默和敲除α-syn或Tau中的一个来探索α-syn或Tau对彼此的影响。我们发现METH增加了SH-SY 5 Y细胞、原代培养的神经元和小鼠脑中的α-syn、总Tau和pSer 396 Tau蛋白水平。此外，降低α-syn水平可以减轻甚至使METH处理后的pSer 396 Tau和总Tau过表达正常化。此外，敲除Tau可以有效抑制METH诱导的小鼠脑中α-syn的过表达。最后，敲除alpha-syn或Tau可以有效地降低小鼠脑中的MET诱导的神经毒性。这项研究可以提供潜在的治疗方法，针对METH滥用者和神经退行性疾病患者中α-syn和Tau之间的恶性循环。
The upregulated alpha-synuclein (alpha-syn) and Tau co-occur in methamphetamine (METH) abusers' brains. Here, we designed experiments mainly to investigate whether alpha-syn and Tau interact in METH exposure. We detected the expression of alpha-syn, total Tau, and phosphorylation of Tau at Serine 396 (pSer396 Tau) under in vitro and in vivo conditions after METH exposure to determine the co-occurrence of alpha-syn and Tau. We also explored the effect of alpha-syn or Tau on one another by silencing and knocking-out one of them in METH treatment. We found that METH increased the alpha-syn, total Tau, and pSer396 Tau protein level in SH-SY5Y cells, primary cultured neurons, and in mice brains. In additional, reducing alpha-syn level can relieve and even normalize the pSer396 Tau and total Tau overexpression after treatment of METH. Furthermore, knocking out Tau can effectively inhibit METH induced overexpression of alpha-syn in mice brains. Finally, knocking out alpha-syn or Tau can effectively reduce METH-induced neurotoxicity in mice brains. This research could provide potential therapeutic approaches targeting the vicious circle between alpha-syn and Tau in METH abusers and patients with neurodegenerative disorders.