Wellington C L, Hayden M R
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
Curr Opin Neurol. 1997 Aug;10(4):291-8. doi: 10.1097/00019052-199708000-00003.
Huntington's disease is caused by expansion of a CAG trinucleotide beyond 35 repeats within the coding region of a novel gene. Recently, new insights into the relationship between CAG expansion in the HD gene and pathological mechanisms have emerged. These include a more precise understanding of the relationship between CAG repeat length and age of onset, progress in transgenic and excitotoxic animal models, identification of a novel huntington-interacting protein, and intriguing connections between huntington and the apoptotic machinery. We have combined many of these new findings into a model that suggests mechanisms and predicts outcomes by which the pathogenesis of Huntington's disease may be initiated. The development of appropriate in-vitro and animal models for Huntington's disease will allow the validity of this model to be tested.
亨廷顿舞蹈症是由一个新基因编码区域内的CAG三核苷酸重复序列扩展至35次以上所引起的。最近，对于亨廷顿舞蹈症（HD）基因中CAG重复序列扩展与病理机制之间的关系有了新的认识。这些认识包括对CAG重复序列长度与发病年龄之间关系的更精确理解、转基因和兴奋性毒性动物模型方面的进展、一种新型亨廷顿相互作用蛋白的鉴定，以及亨廷顿蛋白与凋亡机制之间引人关注的联系。我们将其中许多新发现整合到一个模型中，该模型提出了亨廷顿舞蹈症发病机制可能启动的机制并预测了结果。开发合适的亨廷顿舞蹈症体外和动物模型将使该模型的有效性得到检验。
