Kakizuka A
4th Department, Osaka Bioscience Institute, Japan.
Trends Genet. 1998 Oct;14(10):396-402. doi: 10.1016/s0168-9525(98)01559-5.
Molecular genetic analyses have elucidated a class of inherited neurodegenerative disorders caused by expanded CAG repeats encoding polyglutamines (e.g. Huntington disease and Machado-Joseph disease). Proteins containing expanded polyglutamine repeats appear to precipitate by self-aggregation and, as a result, produce a core disease-related phenotype: neuronal cell death or degeneration. In other neurodegenerative disorders, such as Alzheimer disease, prion disease, Parkinson disease and amyotrophic lateral sclerosis, precipitation of abnormal proteins is also now considered to play a key role. These observations might lead to the elucidation of universal mechanisms for neurodegeneration and to effective treatments for many neurodegenerative disorders.
分子遗传学分析已经阐明了一类由编码多聚谷氨酰胺的CAG重复序列扩增引起的遗传性神经退行性疾病(如亨廷顿舞蹈症和马查多-约瑟夫病)。含有扩增的多聚谷氨酰胺重复序列的蛋白质似乎会通过自我聚集而沉淀,结果产生一种与疾病核心相关的表型:神经元细胞死亡或退化。在其他神经退行性疾病中,如阿尔茨海默病、朊病毒病、帕金森病和肌萎缩侧索硬化症,异常蛋白质的沉淀现在也被认为起着关键作用。这些观察结果可能会导致阐明神经退行性变的普遍机制,并为许多神经退行性疾病找到有效的治疗方法。