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Logo of neuroscibullNeuroscience Bulletin
 
Neurosci Bull. 2010 June; 26(3): 247–256.
Published online 2010 June 3. doi:  10.1007/s12264-010-0113-2
PMCID: PMC5552486

Language: English | Chinese

Current understanding on the pathogenesis of polyglutamine diseases

多聚谷氨酰胺疾病分子发病机制的研究进展

Abstract

Polyglutamine (polyQ) diseases are a family of neurodegenerative disorders including Huntington’s disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias. polyQ diseases are caused by abnormal expansion of CAG repeats in certain genes. The expanded CAG repeats are then translated into a series of abnormally expanded polyQ tracts. Such polyQ tracts may induce misfolding of the disease-causing proteins. The present review mainly focuses on the common characteristics of the pathogenesis of these polyQ diseases, including conformational transition of proteins and its influence on the function of these proteins, the correlation between decreased ability of proteolysis and late-onset polyQ diseases, and the relationship between wide expression of disease-causing proteins and selective neuronal death.

Keywords: polyglutamine, the central nervous system, neurodegenerative diseases, late-onset disorders, ubiquitin, autophagy

摘要

多聚谷氨酰胺疾病是一类中枢神经系统退行性疾病, 目前已知的包括亨廷顿氏舞蹈病、脊延髓肌萎缩症、 齿状核红核苍白球丘脑下部核萎缩以及其它几种脊髓小脑共济失调亚型。 多聚谷氨酰胺疾病是由疾病相关基因的外显子内CAG三核苷酸重复序列异常扩展引起的, 后者导致其编码的多聚谷氨酰胺链的异常延长, 引起相关蛋白质的错误折叠。 本文主要探讨多聚谷氨酰胺疾病分子发病机制的一些共同特征, 包括蛋白质构象变化及其对蛋白功能的影响、 蛋白水解能力下降与疾病迟发性的相互关系以及致病蛋白广泛表达与神经元选择性死亡的关系。

关键词: 多聚谷氨酰胺, 中枢神经系统, 神经退行性疾病, 迟发型障碍, 泛素, 自噬

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