Zoghbi H Y, Orr H T
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Annu Rev Neurosci. 2000;23:217-47. doi: 10.1146/annurev.neuro.23.1.217.
A growing number of neurodegenerative diseases have been found to result from the expansion of an unstable trinucleotide repeat. Over the past 6 years, researchers have focused on identifying the mechanism by which the expanded polyglutamine tract renders a protein toxic to a subset of vulnerable neurons. In this review, we summarize the clinicopathologic features of these disorders (spinobulbar muscular atrophy, Huntington disease, and the spinocerebellar ataxias, including dentatorubropallidoluysian atrophy), describe the genes involved and what is known about their products, and discuss the model systems that have lent insight into pathogenesis. The review concludes with a model for pathogenesis that illuminates the unifying features of these polyglutamine disorders. This model may prove relevant to other neurodegenerative disorders as well.
越来越多的神经退行性疾病被发现是由不稳定的三核苷酸重复序列扩增所致。在过去6年里，研究人员一直致力于确定扩增的聚谷氨酰胺序列致使蛋白质对一部分易损神经元产生毒性的机制。在这篇综述中，我们总结了这些疾病（脊髓延髓肌萎缩症、亨廷顿病以及脊髓小脑共济失调，包括齿状核红核苍白球路易体萎缩症）的临床病理特征，描述了相关基因及其已知产物，并讨论了有助于深入了解发病机制的模型系统。综述最后提出了一个发病机制模型，阐明了这些聚谷氨酰胺疾病的共同特征。该模型可能也与其他神经退行性疾病相关。
