Alpha-synuclein Toxicity in the Early Secretory Pathway: How It Drives Neurodegeneration in Parkinsons Disease.
Alpha-synuclein Toxicity in the Early Secretory Pathway: How It Drives Neurodegeneration in Parkinsons Disease.
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DOI：
10.3389/fnins.2015.00433
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发表时间：
2015
影响因子：
4.3
通讯作者：
Hay JC
中科院分区：
文献类型：
--
作者：
Wang T;Hay JC
α-突触核蛋白是帕金森病发病机制中的主要参与者。然而，尽管广泛的研究了二十年，其生理和病理机制仍然知之甚少。α-突触核蛋白与脂质、运输机制和其他调节因子形成了一个复杂的相互作用网络。一个正在形成的共识是突触囊泡可能是α-突触核蛋白的功能位点，在那里它似乎促进囊泡对接和融合。另一方面，α-突触核蛋白的功能障碍更加分散和众多;当突变或过表达时，α-突触核蛋白影响几种膜运输和应激途径，包括胞吐作用、ER至高尔基体转运、ER应激、高尔基体稳态、内吞作用、自噬、氧化应激等。在这里，我们研究了最近的事态发展α-突触核蛋白的毒性在早期分泌途径的背景下，从其他受影响的途径，以帮助阐明其潜在的致病机制，在神经退行性疾病的新兴主题。
Alpha-synuclein is a predominant player in the pathogenesis of Parkinson's Disease. However, despite extensive study for two decades, its physiological and pathological mechanisms remain poorly understood. Alpha-synuclein forms a perplexing web of interactions with lipids, trafficking machinery, and other regulatory factors. One emerging consensus is that synaptic vesicles are likely the functional site for alpha-synuclein, where it appears to facilitate vesicle docking and fusion. On the other hand, the dysfunctions of alpha-synuclein are more dispersed and numerous; when mutated or over-expressed, alpha-synuclein affects several membrane trafficking and stress pathways, including exocytosis, ER-to-Golgi transport, ER stress, Golgi homeostasis, endocytosis, autophagy, oxidative stress, and others. Here we examine recent developments in alpha-synuclein's toxicity in the early secretory pathway placed in the context of emerging themes from other affected pathways to help illuminate its underlying pathogenic mechanisms in neurodegeneration.