Synucleins in synaptic plasticity and neurodegenerative disorders
Synucleins in synaptic plasticity and neurodegenerative disorders
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DOI：
10.1002/(sici)1097-4547(19991001)58:1
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发表时间：
1999-10-01
影响因子：
4.2
通讯作者：
George, JM
中科院分区：
文献类型：
--
作者：
Clayton, DF;George, JM
突触核蛋白是脊椎动物中高度保守的蛋白质，在神经元中尤其丰富，并且通常在突触前末端富集。人类中的三个基因产生密切相关的突触核蛋白，所有这些蛋白都共享一个大的两亲性结构域，能够可逆地结合到脂质囊泡。α-突触核蛋白与神经退行性疾病特别相关。两个点突变与家族性帕金森病有遗传联系，α突触核蛋白似乎是路易体的主要组成部分。α-突触核蛋白也有助于多系统萎缩的细胞内包涵体，并且在阿尔茨海默病的老年斑中发现了一个片段。虽然它们的正常细胞功能是未知的，但一些观察结果表明突触核蛋白可能用于整合突触前信号传导和膜运输。α突触核蛋白已被鉴定为磷脂酶D2的有效和选择性抑制剂，磷脂酶D2产生磷脂酸（突触核蛋白与其结合），并被认为在细胞表面和细胞内储存之间的膜分配中起作用。我们概述了一个假设，即突触核蛋白支持本地化。突触膜的经验依赖性周转。这样的过程可能对终身学习和记忆功能很重要，并且可能特别容易受到与衰老相关的神经退行性疾病的破坏。(C)1999 Wiley-Liss，Inc.
Synucleins are small highly conserved proteins in vertebrates, especially abundant in neurons and typically enriched at presynaptic terminals. Three genes in humans produce closely related synuclein proteins, all of which share a large amphipathic domain capable of reversible binding to lipid vesicles. Alpha synuclein has been specifically implicated in neurodegenerative disease. Two point mutations are genetically linked to familial Parkinson's disease, and alpha synuclein appears to form the major fibrillary component of Lewy bodies. Alpha synuclein also contributes to the intracellular inclusions of multiple system atrophy, and a fragment has been found in senile plaques in Alzheimer's disease. Although their normal cellular functions are unknown, several observations suggest the synucleins may serve to integrate presynaptic signaling and membrane trafficking, Alpha synuclein has been identified as a potent and selective inhibitor of phospholipase D2, which produces phosphatidic acid (to which synuclein binds) and is believed to function in the partitioning of membranes between the cell surface and intracellular stores. We outline a hypothesis whereby synuclein supports localized. experience-dependent turnover of synaptic membranes. Such a process may be important for lifelong learning and memory functions and may be especially vulnerable to disruption in aging-associated neurodegenerative diseases. (C) 1999 Wiley-Liss, Inc.