遗传性痉挛性截瘫4型发病机制的研究进展

发布时间：2018-03-08 07:41

本文选题：遗传性痉挛性截瘫　切入点：痉挛性截瘫型　出处：《上海交通大学学报(医学版)》2017年09期 　论文类型：期刊论文

【摘要】：遗传性痉挛性截瘫(HSP)是一类具有显著临床和遗传异质性的神经退行性疾病,主要临床表现为缓慢进展的双下肢无力和痉挛性截瘫,其中以痉挛性截瘫4型(SPG4)最为常见。迄今,已发现78个HSP致病基因相关位点,59个致病基因被克隆。基因SPAST编码的微管切割蛋白(spastin)对于调节微管长度、数量和活力,以及对各种细胞器的发生、发展都具有重要意义。过去认为SPAST基因突变导致所编码的蛋白功能部分或全部丧失,是疾病发生的主要机制。目前认为,SPAST基因编码的2种异构体(M1、M87)可能存在获得性的突变蛋白的神经毒性作用,也是重要致病机制之一。该文就SPG4的发病机制进行综述。
[Abstract]:Hereditary spastic paraplegia (HSP) is a class of neurodegenerative diseases with significant clinical and genetic heterogeneity. The main clinical manifestations are slow progression of lower extremity weakness and spastic paraplegia, of which spastic paraplegia type 4 (SPG4) is the most common. Seventy-eight HSP pathogenetic genes have been identified, and 59 pathogenetic genes have been cloned. The microtubule-cutting protein encoded by gene SPAST, spastin, regulates the length, number and activity of microtubules, as well as the occurrence of various organelles. It used to be thought that mutations in the SPAST gene led to partial or total loss of the function of the encoded protein. At present, it is considered that the two isomers encoded by the SPAST gene may have the neurotoxicity of acquired mutant protein, which is also one of the important pathogenetic mechanisms. The pathogenesis of SPG4 is reviewed in this paper.
【作者单位】：上海交通大学医学院附属瑞金医院神经内科神经病学研究所;
【基金】：国家自然科学基金(81571086) 上海市教育委员会高峰高原学科建设计划(20161401) 上海交通大学“医工交叉研究基金”资助项目(YG2016MS64)~~
【分类号】：R741

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