Feigin A
Movement Disorders Center, Manhassel, NY 11030, USA.
Curr Opin Neurol. 1998 Aug;11(4):357-62. doi: 10.1097/00019052-199808000-00012.
The gene mutation causing Huntington's disease was identified in 1993 as an expanded trinucleotide repeat within the coding region for a 348-kd protein called huntingtin. The mechanism by which this cytosine-adenosine-guanosine repeat produces the progressive signs and symptoms of Huntington's disease remains uncertain, but recent advances have begun to provide insights into this process. Promising developments include transgenic mouse models of Huntington's disease with neuronal intranuclear inclusions, the identification of differential neuronal features which might account for the selective vulnerability of neurons seen in Huntington's disease and further evidence for the role of excitotoxicity and impaired mitochondrial energy production. These observations have suggested new therapeutic strategies, and have lent further support for experimental therapeutics aimed at improving mitochondrial function and reducing excitotoxic injury.
1993年，导致亨廷顿舞蹈症的基因突变被确定为一种名为亨廷顿蛋白的348千道尔顿蛋白质编码区域内的三核苷酸重复序列扩增。这种胞嘧啶-腺嘌呤-鸟嘌呤重复序列导致亨廷顿舞蹈症进行性体征和症状的机制仍不明确，但最近的进展已开始为这一过程提供见解。有前景的进展包括具有神经元核内包涵体的亨廷顿舞蹈症转基因小鼠模型、对可能解释亨廷顿舞蹈症中所见神经元选择性易损性的不同神经元特征的识别，以及兴奋性毒性和线粒体能量产生受损作用的进一步证据。这些观察结果提示了新的治疗策略，并为旨在改善线粒体功能和减少兴奋性毒性损伤的实验性治疗提供了进一步支持。
