The Parkinson's Disease-Associated Protein α-Synuclein Disrupts Stress Signaling - A Possible Implication for Methamphetamine Use?
The Parkinson's Disease-Associated Protein α-Synuclein Disrupts Stress Signaling - A Possible Implication for Methamphetamine Use?
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DOI：
10.15698/mic2014.04.137
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Witt SN
中科院分区：
文献类型：
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作者：
Wang S;Witt SN
人类神经元蛋白α-突触核蛋白（α-syn）已被大量研究认为是散发性帕金森病（PD）的致病因素。为了加快发现α-syn的生物学和病理学的步伐，酵母、蠕虫和苍蝇等生物体已被用于研究α-syn水平升高对细胞有毒的机制，并筛选抑制这种毒性的药物和基因。我们最近报道了[Wang等人，Proc. Natl. Acad. Sci.（2012）109：16119-16124]，人α-syn在高表达水平下破坏酵母和人神经母细胞瘤细胞中的应激激活的信号转导途径。这些信号通路的破坏最终导致对压力的脆弱性和细胞死亡。在这里，我们讨论了α-syn对细胞信号的破坏如何与帕金森综合征有关，帕金森综合征与滥用药物甲基苯丙胺（冰毒）有关。
The human neuronal protein α-synuclein (α-syn) has been linked by a plethora of studies as a causative factor in sporadic Parkinson’s disease (PD). To speed the pace of discovery about the biology and pathobiology of α-syn, organisms such as yeast, worms, and flies have been used to investigate the mechanisms by which elevated levels of α-syn are toxic to cells and to screen for drugs and genes that suppress this toxicity. We recently reported [Wang et al. Proc. Natl. Acad. Sci. (2012) 109: 16119-16124] that human α-syn, at high expression levels, disrupts stress-activated signal transduction pathways in both yeast and human neuroblastoma cells. Disruption of these signaling pathways ultimately leads to vulnerability to stress and to cell death. Here we discuss how the disruption of cell signaling by α-syn may have relevance to the parkinsonism that is associated with the abuse of the drug methamphetamine (meth).