脊髓小脑共济失调3型致病蛋白ataxin-3毒性损伤机制  

The toxic effect of expanded ataxin-3 in spinocerebellar ataxia type 3

作　　者：冯黎[1] 陈定邦[1] 林晓浦[1] 李洵桦 

机构地区：[1]中山大学附属第一医院神经内科,广州510080 [2]南方医院神经内科,广州510515

出　　处：《国际遗传学杂志》2012年第5期290-294,共5页International Journal of Genetics

基　　金：基金项目：国家自然科学基金项目（81171070）

摘　　要：脊髓小脑共济失调3型是我国常见的三核苷酸序列异常扩增导致的常染色体显性遗传疾病。其致病蛋白ataxin-3具有泛素结合蛋白功能，调节细胞蛋白质稳态；同时ataxin-3蛋白功能可能还与细胞骨架等相关。异常扩展突变的ataxin-3有聚集倾向，在细胞内募集多种蛋白成分形成蛋白聚集体或包涵体，导致基因转录异常、蛋白稳态失衡、能量代谢障碍、运输障碍等多种细胞功能损伤以致细胞凋亡，进而影响细胞功能而致病。结合目前对多聚谷氨酸异常扩展突变疾病的研究现状，此文就现有的脊髓小脑共济失调3型致病机制进行综述。The spinocerebellar ataxia-type 3 （SCA3） , which belongs to the group of polyglu- tamine repeat （ polyQ ） diseases, is the most frequent form among the autosomal dominantly inherited spinocerebellar ataxias in China. Ataxin-3, encoded by SCA3 gene （ atxn3 ） , is a ubiqitin-bingding protein and involved in mornitoring the degenaration of proteins by its deubiquitylation activity. The expanded ataxin-3 is of aggregative potential and forms aggresomes or inclusions by recruiting other proteins. The mutant ataxin-3 compromises the regulation of transcription, challenges the cell＇ s ability to keep up with protein degradation, interferes with cellular metabolism and transportion, and eventually leads to cell apoptosis. This review will focus on emerging concepts of PolyQ disease, emphasizing the pathogenesis of SCA3.

关 键 词：脊髓小脑共济失调 ATAXIN-3 毒性机制 

分 类 号：R744.7[医药卫生—神经病学与精神病学]