α-Synuclein蛋白聚集状态与帕金森病形成  

Aggregation States of α-Synuclein and Its Involvement in Parkinson’s Disease

作　　者：王丹晨[1] 于珊珊[1] 刘巍峰[1] 陈冠军[1] 

机构地区：[1]山东大学生命科学学院,济南250100

出　　处：《中国生物化学与分子生物学报》2006年第8期615-620,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：山东省优秀中青年科学家奖励基金资助项目(2004B302011)~~

摘　　要：帕金森病是一种常见的老年神经退行性疾病,其致病机理复杂.其中α-synuclein基因是较早发现的与帕金森病相关的基因,其编码的α-synuclein蛋白是帕金森病神经元内出现的一种蛋白包涵体结构——路易体的主要组成成分.最近的研究结果显示,α-synuclein蛋白存在不同聚集状态间的转换,其中聚集过程中形成的寡聚体中间构象具有较强的细胞毒性,可能对帕金森病的发病过程有着重要作用;而且这种聚集状态的转换过程受到多种遗传学与细胞学因素的影响,从而在某种程度上反映了帕金森病发生形成的遗传学与细胞学机制.本文将对α-synuclein蛋白聚集状态转换特性及其在帕金森病发病过程中作用机制方面的研究进展作一综述.Parkinson＇ s disease （PD） is a wide-spread age-related neurodegeneration disorder with very complex pathological mechanisms, α-Synuclein gene is among the first genes identified to be related to PD and the α-synuclein protein is a major component of protein inclusions called Lewy bodies, whose appearance in the survival dopamine neurons is one of the pathologic hallmarks of PD. α-synuclein has recently been shown to undergo transitions between different aggregation states both in vivo and in vitro, mediated by the readily aggregated propensity of α-synuclein. Among others, an intermediate oligomer configuration called protofibril, has been found to show much stronger cytotoxicity than the insoluble fibril conformation, which is the final form of polymerization normally found in Lewy bodies. In the meantime, quite a few genetic and cellular factors including α-synuclein gene mutation and duplication, lipid metabolism, oxidative stress as well as protein folding and quality control system, have been demonstrated to affect the process of α-synuclein aggregation. These findings are beginning to uncover the underlying mechanisms of the occurrence and development of PD. Herein, we review recent findings on the structural characterization of α-synuclein and exploit the possible molecular and cellular mechanisms involved in the etiopathogenesis of PD.

关 键 词：帕金森病 α-synuclein蛋白 蛋白聚集 不饱和脂肪酸 泛素-蛋白酶体 

分 类 号：Q71[生物学—分子生物学] Q426