脆性X综合征致病机理与治疗  

Pathogenesis and treatment of fragile X syndrome

作　　者：马云 李婉睿 刘伊煊 姜志胜 何淑雅 MA Yun;LI Wanrui;LIU Yixuan;JIANG Zhisheng;HE Shuya(Hengyang Medical College,University of South China,Hengyang 421001,China;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study,Hengyang 421001,China)

机构地区：[1]南华大学衡阳医学院,衡阳421001 [2]湖南省分子靶向新药研究合作创新中心,衡阳421001

出　　处：《生命的化学》2020年第2期192-197,共6页Chemistry of Life

基　　金：国家自然科学基金项目(81971087);湖南省研究生创新基金项目(CX2018B624)。

摘　　要：脆性X综合征(fragile X syndrome, FXS)是最常见的遗传性智力障碍疾病,主要是由于X染色体上脆性X智力低下基因1(fragile X-mental retardation gene 1, FMR1)5’端非翻译区CGG三核苷酸的重复扩增及其相邻部位CpG岛的异常甲基化而导致其编码产物脆性X智力低下蛋白(fragile X mental retardation protein, FMRP)的缺失引起。目前,基因诊断已成为FXS诊断的金标准,但临床治疗仍缺乏特异性。本文首先介绍了FMRP的结构与功能,剖析了FXS的致病机制,然后阐述了FXS中与FMRP表达相关的信号转导途径,深入探讨并总结了靶向干预FXS中信号通路、基因编辑逆转FMR1沉默以及靶向降解FXS异常表达蛋白的治疗策略。Fragile X syndrome(FXS), the most common hereditary mental disorders, is mainly caused by amplification of CGG trinucleotide repeat in the 5’-untranslated region of fragile X-mental retardation gene 1(FMR1) on the X chromosome and the abnormal methylation of CpG island in its adjacent region, which results in the deletion of its protein product fragile X mental retardation protein(FMRP). Currently, gene diagnosis has become the gold standard of FXS diagnosis, but it is still lack of specificity in clinical treatment. This review firstly introduced the structure and function of FMRP, and analyzed the pathogenic mechanism of FXS;then summerized the signal transduction pathway related to FMRP in FXS, deeply discussed the treatment strategies of targeted intervention of signal pathway in FXS, gene editing to reverse FMR1 silencing and targeted degradation of FXS abnormal expression protein.

关 键 词：FXS 信号通路 治疗研究 

分 类 号：R749[医药卫生—神经病学与精神病学]