The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias.
The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias.
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DOI：
10.1186/1471-2091-8-s1-s2
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发表时间：
2007-11-22
期刊：
影响因子：
--
通讯作者：
Rubinsztein DC
中科院分区：
文献类型：
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作者：
Davies JE;Sarkar S;Rubinsztein DC
亨廷顿病和几种脊髓小脑共济失调是由疾病基因编码区内CAG重复序列的异常扩增引起的。这导致产生具有异常扩展的多聚谷氨酰胺束的突变蛋白。虽然这些疾病有一个明确的单基因原因，每个多聚谷氨酰胺扩增突变可能会导致细胞内的许多途径和过程的功能障碍。已经提出，泛素蛋白酶体系统在多聚谷氨酰胺扩增障碍中受损，并且这有助于病理学。然而，这是有争议的，一些组证明在多聚谷氨酰胺扩增疾病中蛋白酶体活性降低，一些组显示活性无变化，另一些组显示蛋白酶体活性增加。它仍然是未知的泛素蛋白酶体系统是否是一个可行的治疗目标，在这些疾病。在这里，我们回顾了在各种不同的系统中进行的不同测定所获得的相互矛盾的结果。出版历史：从Current BioData的靶向蛋白质数据库（TPdb;）重新出版。
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; ).