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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。
Polyglutamine diseases are a group of central nervous system degenerative diseases that are known to date include Huntington’s disease, spinobulbar muscular atrophy, nucleus atrophy of the dentate nucleus pallidolutrium, and several other Spinocerebellar Atypical subtypes. Polyglutamine disease is caused by abnormal expansion of exon CAG trinucleotide repeats of disease-associated genes, which leads to an abnormal prolongation of its encoded polyglutamine chains, causing misfolding of related proteins . This article focuses on some common features of molecular pathogenesis of polyglutamine disease, including changes in protein conformation and its effects on protein function, the relationship between decreased proteolysis and delayed disease, and the extensive expression of pathogenic proteins and neurons Selective death of the relationship.