Hannan Anthony J
Howard Florey Institute, National Neuroscience Facility, University of Melbourne, Parkville, VIC 3010, Australia.
Expert Opin Ther Targets. 2005 Aug;9(4):639-50. doi: 10.1517/14728222.9.4.639.
Huntington's disease (HD) is a fatal autosomal-dominant disorder involving progressive motor, cognitive and psychiatric symptoms. HD is one of a large family of neurodegenerative diseases caused by a trinucleotide (CAG) repeat mutation, encoding an expanded tract of glutamines in the disease protein. HD was one of the first neurological disorders for which accurate transgenic models were created, allowing mechanisms of pathogenesis to be explored at molecular, cellular and behavioural levels. In the last decade, the understanding of molecular and cellular changes which occur in HD prior to onset of symptoms, and at early and late stages of disease progression, has been greatly expanded. A wide range of potential molecular targets for therapeutic intervention have been identified, associated with a variety of cellular processes including gene transcription, protein trafficking, protein degradation, protein-protein interactions, glutamatergic synaptic transmission, presynaptic signalling, postsynaptic signalling, synaptic plasticity, dopaminergic and neurotrophic modulation of synaptic function, experience-dependent neurogenesis, mitochondrial function and oxidative metabolism. Presymptomatic testing for the HD gene mutation necessitates future development of novel therapeutics aimed at delaying onset of symptoms, as well as slowing or reversing disease progression.
亨廷顿舞蹈症（HD）是一种致命的常染色体显性疾病，会导致进行性运动、认知和精神症状。HD是由三核苷酸（CAG）重复突变引起的一大类神经退行性疾病之一，该突变导致疾病蛋白中谷氨酰胺序列延长。HD是最早创建出精确转基因模型的神经疾病之一，这使得在分子、细胞和行为水平上探索发病机制成为可能。在过去十年中，对于HD在症状出现之前以及疾病进展的早期和晚期所发生的分子和细胞变化的理解有了极大的扩展。已经确定了广泛的潜在治疗干预分子靶点，这些靶点与多种细胞过程相关，包括基因转录、蛋白质运输、蛋白质降解、蛋白质-蛋白质相互作用、谷氨酸能突触传递、突触前信号传导、突触后信号传导、突触可塑性、多巴胺能和神经营养对突触功能的调节、经验依赖性神经发生、线粒体功能和氧化代谢。对HD基因突变进行症状前检测需要未来开发旨在延迟症状出现以及减缓或逆转疾病进展的新型疗法。
