论文部分内容阅读
C9orf72突变是导致肌萎缩侧索硬化症和额颞叶痴呆最主要的突变形式,该突变由GGGGCC长重复序列插入C9orf72基因的内含子中造成.该突变有3种致病机制:由C9orf72蛋白表达量降低造成的功能缺失、长重复序列RNA造成的细胞毒性、长重复RNA转录产物造成的细胞毒性.本文就从3个方面综合分析了该突变的分子学致病机制,从RNA和蛋白质代谢以及核仁应激三方面总结了3种致病机制之间的联系,并对该突变致病机制研究遇到的困难和未来发展方向进行了总结和预测.
The C9orf72 mutation is the most predominant mutation that leads to amyotrophic lateral sclerosis and frontotemporal dementia resulting from the insertion of the GGGGCC long repeat into the intron of the C9orf72 gene.This mutation has three pathogenic mechanisms: the C9orf72 protein Loss of function caused by decreased expression, cytotoxicity caused by long repeated RNA, and cytotoxicity caused by long repeated RNA transcripts.In this paper, the molecular pathogenesis of this mutation was comprehensively analyzed from three aspects: RNA and protein metabolism And nuclear stress in three aspects summarized the relationship between the three pathogenic mechanisms, and the mutation pathogenic mechanism of the difficulties encountered and the future direction of development were summarized and predicted.