Methamphetamine exposure induces neuropathic protein β-Amyloid expression
Methamphetamine exposure induces neuropathic protein β-Amyloid expression
复制标题
甲基苯丙胺暴露诱导神经病性蛋白β-淀粉样蛋白表达
DOI：
10.1016/j.tiv.2018.10.012
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发表时间：
2019-02-01
影响因子：
3.2
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Chen, Lingling;Yu, Pengfei;Wang, Jun
甲基苯丙胺（冰毒）滥用会导致多巴胺能神经元退化，导致帕金森病（PD）样变化。最近，甲基苯丙胺暴露与阿尔茨海默病（AD）样变化之间的关系得到了更多的关注，然而，其潜在机制仍然知之甚少。在本研究中，我们旨在研究甲基安非他明暴露是否会促进A β(42)的形成，A β是关键的ad样病理蛋白之一。在细胞模型PC-12细胞系中，甲基苯甲胺处理显著提高了前体蛋白APP及其水解产物CTFs的表达水平，且呈剂量依赖性。与此同时，通过ELISA检测，我们发现甲基安非他明暴露导致细胞培养上清中A β(42)排泄明显升高。因此，我们检测了分别负责APP和A β(42)生成的p-GSK3 α和BACE-1的表达，结果表明，甲基甲基苯丙胺明显激活了p-GSK3 α，增加了BACE-1的水平，同时免疫荧光检测了BACE-1的表达，BACE-1的荧光强度显著升高。综上所述，甲基苯丙胺处理促进了A β前体蛋白APP及其水解产物CTFs和A β(1-42)的表达，p-GSK3 α和BACE-1可能参与了这一过程。
Methamphetamine (METH) abusing contributes to dopaminergic neurons degeneration, resulting inParkinson's disease (PD)-like changes. More recently, the association between METH exposure and the Alzheimer's disease (AD)-like changes gained more attention, however, the underlying mechanisms remain poorly understood. In the present study, we aimed to investigate whether METH exposure promotes the formation of A beta(42), one of the key AD-like pathological proteins. With the cell model PC-12 cell line, it showed that METH treatment significantly increased the level of the precursor protein APP and its hydrolysates CTFs expression in a dose-dependent manner. In parallel, with the ELISA assay, we found that METH exposure contributed to an obvious elevation of the A beta(42) excretion in the cell culture supernatant. Therefore, we examined the expression of p-GSK3 alpha and BACE-1, which were responsible for APP and A beta(42) generation respectively, it suggested in that METH obviously activated the p-GSK3 alpha and increased the level of BACE-1, and the expression of BACE-1 was also detected by the immunofluorescence, with the significant elevation of the BACE-1 fluorescence intensity. In conclusion, METH treatment promotes the expression of A beta precursor protein APP and its hydrolysis product CTFs and A beta(1-42), and p-GSK3 alpha as well as BACE-1 may be involved in this process.