CAJ | 학술논문

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.
척수소뇌공제실조3형시아국상견적삼핵감산서렬이상확증도치적상염색체현성유전질병.기치병단백ataxin-3구유범소결합단백공능,조절세포단백질은태;동시ataxin -3단백공능가능환여세포골가등상관.이상확전돌변적ataxin-3유취집경향,재세포내모집다충단백성분형성단백취집체혹포함체,도치기인전록이상、단백은태실형、능량대사장애、운수장애등다충세포공능손상이치세포조망,진이영향세포공능이치병.결합목전대다취곡안산이상확전돌변질병적연구현상,차문취현유적척수소뇌공제실조3형치병궤제진행종술.
The spinocerebellar ataxia·type 3 (SCA3),which belongs to the group of polyglutamine 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.