Departments of Psychiatry, Neurology, Pharmacology, and Neuroscience, and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lancet Neurol. 2011 Jan;10(1):83-98. doi: 10.1016/S1474-4422(10)70245-3.
Huntington's disease is a progressive, fatal, neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene, which encodes an abnormally long polyglutamine repeat in the huntingtin protein. Huntington's disease has served as a model for the study of other more common neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. These disorders all share features including: delayed onset; selective neuronal vulnerability, despite widespread expression of disease-related proteins during the whole lifetime; abnormal protein processing and aggregation; and cellular toxic effects involving both cell autonomous and cell-cell interaction mechanisms. Pathogenic pathways of Huntington's disease are beginning to be unravelled, offering targets for treatments. Additionally, predictive genetic testing and findings of neuroimaging studies show that, as in some other neurodegenerative disorders, neurodegeneration in affected individuals begins many years before onset of diagnosable signs and symptoms of Huntington's disease, and it is accompanied by subtle cognitive, motor, and psychiatric changes (so-called prodromal disease). Thus, Huntington's disease is also emerging as a model for strategies to develop therapeutic interventions, not only to slow progression of manifest disease but also to delay, or ideally prevent, its onset.
亨廷顿病是一种进行性、致命的神经退行性疾病，由亨廷顿基因中的 CAG 重复扩增引起，该基因编码亨廷顿蛋白中的异常长的多谷氨酰胺重复。亨廷顿病一直是研究其他更常见的神经退行性疾病（如阿尔茨海默病和帕金森病）的模型。这些疾病都具有以下特征：发病较晚；尽管在整个生命周期中广泛表达与疾病相关的蛋白质，但选择性神经元易损性；异常蛋白加工和聚集；以及涉及细胞自主和细胞间相互作用机制的细胞毒性效应。亨廷顿病的发病机制正在被揭示，为治疗提供了靶点。此外，遗传预测测试和神经影像学研究结果表明，与其他一些神经退行性疾病一样，在可诊断的亨廷顿病症状和体征出现之前的许多年，受影响个体的神经退行性变就已经开始，并且伴随着微妙的认知、运动和精神变化（所谓的前驱疾病）。因此，亨廷顿病也正在成为开发治疗干预策略的模型，不仅可以减缓显性疾病的进展，还可以延迟（理想情况下预防）其发病。
