Wanker E E
Max-Planck-Institut für Molekulare Genetik, Berlin, Germany.
Biol Chem. 2000 Sep-Oct;381(9-10):937-42. doi: 10.1515/BC.2000.114.
The formation of insoluble protein aggregates is a hallmark of Huntington's disease (HD) and related neurodegenerative disorders, such as dentatorubral pallidoluysian atrophy (DRPLA), spinal bulbar muscular atrophy (SBMA) and the spinocerebellar ataxia (SCA) type 1, 2, 3, 6 and 7. These disorders are caused by an expanded polyglutamine (polyQ) tract in otherwise unrelated proteins. They are characterized by late-onset, selective neuropathology, a pathogenic polyQ threshold and a relationship between polyQ length and disease progression. Thus, molecular models of HD and related glutamine-repeat disorders must account for these characteristic features. During the last three years, considerable effort has been invested in the development of in vitro and in vivo model systems to study the mechanisms of protein aggregation in glutamine-repeat disorders and its potential effects on disease progression and neurodegeneration. A selection of these studies is reviewed here. Furthermore, the correlation between aggregate formation and development of HD is discussed.
不溶性蛋白质聚集体的形成是亨廷顿舞蹈症（HD）及相关神经退行性疾病的一个标志，这些相关疾病包括齿状核红核苍白球路易体萎缩症（DRPLA）、脊髓延髓肌萎缩症（SBMA）以及1型、2型、3型、6型和7型脊髓小脑共济失调症（SCA）。这些疾病是由原本不相关的蛋白质中多聚谷氨酰胺（polyQ）序列的扩增所引起的。它们具有发病较晚、选择性神经病理学特征、致病的polyQ阈值以及polyQ长度与疾病进展之间的关系等特点。因此，HD及相关谷氨酰胺重复序列疾病的分子模型必须考虑到这些特征。在过去三年中，人们投入了大量精力来开发体外和体内模型系统，以研究谷氨酰胺重复序列疾病中蛋白质聚集的机制及其对疾病进展和神经退行性变的潜在影响。本文将对其中一些研究进行综述。此外，还将讨论聚集体形成与HD发展之间的相关性。
