Davies Janet E, Sarkar Sovan, Rubinsztein David C
Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK.
BMC Biochem. 2007 Nov 22;8 Suppl 1(Suppl 1):S2. doi: 10.1186/1471-2091-8-S1-S2.
Huntington's disease and several of the spinocerebellar ataxias are caused by the abnormal expansion of a CAG repeat within the coding region of the disease gene. This results in the production of a mutant protein with an abnormally expanded polyglutamine tract. Although these disorders have a clear monogenic cause, each polyglutamine expansion mutation is likely to cause the dysfunction of many pathways and processes within the cell. It has been proposed that the ubiquitin proteasome system is impaired in polyglutamine expansion disorders and that this contributes to pathology. However, this is controversial with some groups demonstrating decreased proteasome activity in polyglutamine expansion disorders, some showing no change in activity and others demonstrating an increase in proteasome activity. It remains unknown whether the ubiquitin proteasome system is a feasible therapeutic target in these disorders. Here we review the conflicting results obtained from different assays performed in a variety of different systems. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
亨廷顿舞蹈症和几种脊髓小脑共济失调症是由疾病基因编码区内CAG重复序列的异常扩增所引起的。这导致产生一种具有异常扩增的聚谷氨酰胺序列的突变蛋白。尽管这些疾病有明确的单基因病因，但每个聚谷氨酰胺扩增突变可能会导致细胞内许多通路和过程的功能障碍。有人提出泛素蛋白酶体系统在聚谷氨酰胺扩增疾病中受损，且这促成了病理学变化。然而，这存在争议，一些研究小组表明聚谷氨酰胺扩增疾病中蛋白酶体活性降低，一些显示活性无变化，还有一些表明蛋白酶体活性增加。泛素蛋白酶体系统在这些疾病中是否是一个可行的治疗靶点仍不清楚。在此，我们综述了在各种不同系统中进行的不同检测所获得的相互矛盾的结果。出版历史：重新发表自Current BioData的靶向蛋白质数据库（TPdb；http://www.targetedproteinsdb.com）。
