Tsuji S
Department of Neurology, Niigata University.
Intern Med. 1997 Jan;36(1):3-8. doi: 10.2169/internalmedicine.36.3.
Expansion of trinucleotide repeats has been identified as a common mechanism of hereditary neurodegenerative diseases including spinal and bulbar muscular atrophy (SBMA), Huntington's disease, dentatorubral-pallidoluysian atrophy (DRPLA), Machado-Joseph disease (MJD), fragile X syndrome, myotonic dystrophy and Friedreich's ataxia. These diseases share unique features, which are difficult to explain based on Mendelian inheritance. These unique clinical genetic features include genetic anticipation and a broad spectrum of clinical presentations, which have been shown to be associated with the instability of the trinucleotide repeats. Recent studies suggest that gene products with expanded polyglutamine tracts may be toxic to neuronal cells, and the mechanisms of neurotoxicity should be thoroughly investigated. To develop therapeutic measures, creation of animal models or cell culture systems for the investigation of neurotoxicity will be indispensable.
三核苷酸重复序列的扩增已被确定为遗传性神经退行性疾病的常见机制，这些疾病包括脊髓延髓性肌萎缩症（SBMA）、亨廷顿舞蹈病、齿状核红核苍白球路易体萎缩症（DRPLA）、马查多-约瑟夫病（MJD）、脆性X综合征、强直性肌营养不良症和弗里德赖希共济失调症。这些疾病具有独特的特征，基于孟德尔遗传很难解释。这些独特的临床遗传特征包括遗传早现和广泛的临床表现谱，已证明这些特征与三核苷酸重复序列的不稳定性有关。最近的研究表明，具有扩展的聚谷氨酰胺序列的基因产物可能对神经元细胞有毒性，神经毒性机制应进行深入研究。为了开发治疗措施，创建用于研究神经毒性的动物模型或细胞培养系统将是必不可少的。
