Ryu Hoon, Ferrante Robert J
Boston University School of Medicine, Edith Nourse Rogers Veterans Administration Medical Center, Bedford, Massachusetts 01730, USA.
Expert Opin Emerg Drugs. 2005 May;10(2):345-63. doi: 10.1517/14728214.10.2.345.
Huntington's disease (HD) is a progressive and fatal neurological disorder caused by an expanded CAG repeat in the gene coding for the protein, huntingtin. There is no clinically proven treatment for HD. Although the exact cause of neuronal death in HD remains unknown, it has been postulated that the abnormal aggregation of the mutant huntingtin protein may cause toxic effects in neurons, leading to a cascade of pathogenic mechanisms associated with transcriptional dysfunction, oxidative stress, mitochondrial alterations, apoptosis, bioenergetic defects and subsequent excitotoxicity. Understanding how these processes interrelate has become important in identifying a pharmacotherapy in HD and in the design of clinical trials. A number of drug compounds that separately target these mechanisms have significantly improved the clinical and neuropathological phenotype of HD transgenic mice and, as such, are immediate candidates for human clinical trials in HD patients. These compounds are discussed herein.
亨廷顿舞蹈症（HD）是一种进行性致命性神经疾病，由编码亨廷顿蛋白的基因中CAG重复序列扩增所致。目前尚无经临床验证的HD治疗方法。尽管HD中神经元死亡的确切原因尚不清楚，但据推测，突变型亨廷顿蛋白的异常聚集可能会对神经元产生毒性作用，导致一系列与转录功能障碍、氧化应激、线粒体改变、细胞凋亡、生物能量缺陷及随后的兴奋性毒性相关的致病机制。了解这些过程如何相互关联，对于确定HD的药物治疗方法以及设计临床试验变得至关重要。一些分别针对这些机制的药物化合物已显著改善了HD转基因小鼠的临床和神经病理学表型，因此，它们是HD患者人类临床试验的直接候选药物。本文将对这些化合物进行讨论。
