Reddy P H, Williams M, Tagle D A
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Trends Neurosci. 1999 Jun;22(6):248-55. doi: 10.1016/s0166-2236(99)01415-0.
Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder that is characterized by abnormal involuntary movements (chorea), intellectual impairment and selective neuronal loss. The expansion of a polymorphic trinucleotide repeat (the sequence CAG that codes for glutamine) to a length that exceeds 40 repeat units in exon 1 of the gene, HD, correlates with the onset and progression of the disease. The protein encoded by HD, huntingtin, is normally localized in the cytoplasm, whereas the mutant protein is also found in the nucleus, suggesting that its translocation to this site is important for the pathogenesis of HD. Although several proteins that interact with huntingtin have been identified in vitro, the significance of these interactions with the mutant protein in the pathogenesis of HD has yet to be determined. Recent progress in the development of cellular and animal models for the disease have provided invaluable insights and resources for studying the disease mechanisms underlying HD, and will be useful for screening and evaluating possible therapeutic strategies.
亨廷顿舞蹈症（HD）是一种常染色体显性遗传的神经退行性疾病，其特征为异常的不自主运动（舞蹈症）、智力障碍和选择性神经元丧失。基因HD外显子1中多态性三核苷酸重复序列（编码谷氨酰胺的CAG序列）扩展至超过40个重复单元的长度，与该疾病的发病和进展相关。HD编码的蛋白质亨廷素通常定位于细胞质中，而突变蛋白也存在于细胞核中，这表明其易位至该位点对HD的发病机制很重要。尽管已在体外鉴定出几种与亨廷素相互作用的蛋白质，但这些与突变蛋白的相互作用在HD发病机制中的意义尚未确定。该疾病的细胞和动物模型开发方面的最新进展为研究HD潜在的疾病机制提供了宝贵的见解和资源，将有助于筛选和评估可能的治疗策略。
