肌萎缩侧索硬化症遗传学机制研究进展

doi:10.3969/j.issn.1672-6731.2023.03.017

中国现代神经疾病杂志 ›› 2023, Vol. 23 ›› Issue (3): 264-269. doi: 10.3969/j.issn.1672-6731.2023.03.017

• 综述 • 上一篇

2 肌萎缩侧索硬化症遗传学机制研究进展

赵倩倩¹, 李宛真¹, 唐北沙^1,2,3, 王俊岭^1,2,3

1 410008 长沙, 中南大学湘雅医院神经内科;
2 410008 长沙, 国家老年疾病临床医学研究中心;
3 410078 长沙, 中南大学医学遗传学研究中心

收稿日期:2023-01-27 出版日期:2023-03-25 发布日期:2023-04-10
通讯作者: 王俊岭,Email:wjling8002@126.com
基金资助:
国家重点研发计划项目（项目编号：2021YFA0805202）；国家重点研发计划项目（项目编号：2018YFC1312003）；国家自然科学基金资助项目（项目编号：82171431）；国家自然科学基金资助项目（项目编号：81671120）；湖南省自然科学基金-杰出青年基金资助项目（项目编号：2020JJ2057）；国家老年疾病临床医学研究中心（湘雅医院）临床研究基金资助项目（项目编号：2020LNJJ13）；中南大学研究生教育教学改革资助项目（项目编号：2020JGB136）

Advances on the genetic mechanism of amyotrophic lateral sclerosis

ZHAO Qian-qian¹, LI Wan-zhen¹, TANG Bei-sha^1,2,3, WANG Jun-ling^1,2,3

1 Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hu'nan, China;
2 National Clinical Research Center for Geriatric Diseases, Changsha 410008, Hu'nan, China;
3 Medical Genetics Research Center, Central South University, Changsha 410078, Hu'nan, China

Received:2023-01-27 Online:2023-03-25 Published:2023-04-10
Supported by:
This study was supported by National Key Research and Development Program of China (No. 2021YFA0805202, 2018YFC1312003), the National Natural Science Foundation of China (No. 82171431, 81671120), Natural Science Fund for Distinguished Young Scholars of Hu'nan (No. 2020JJ2057), Clinical Research Project of National Clinical Research Center for Geriatric Diseases (No. 2020LNJJ13), and Graduate Education and Teaching Reform Project of Central South University (No. 2020JGB136).

摘要/Abstract

摘要： 肌萎缩侧索硬化症是一组选择性侵犯运动神经元的神经系统变性疾病。随着基因检测技术的迅速发展，肌萎缩侧索硬化症基因检测从单基因位点测序逐步发展至全外显子组测序或全基因组测序，越来越多影响疾病发生发展的致病基因相继被发现。目前肌萎缩侧索硬化症病理生理学机制主要包括蛋白稳态失衡、DNA 或RNA 功能异常、细胞骨架和轴突动力学改变、自噬过程和溶酶体功能紊乱、线粒体功能障碍，探究肌萎缩侧索硬化症遗传学机制对阐明其病理生理学机制具有重要意义。本文综述肌萎缩侧索硬化症主要致病基因、遗传学研究方法及相关致病机制，为肌萎缩侧索硬化症治疗提供新的策略。

关键词: 肌萎缩侧索硬化, 运动神经元病, 遗传学, 综述

Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive involvement of upper motor neuron (UMN) and lower motor neuron (LMN). With the rapid development of sequencing technique, genetic screening of ALS improved from a single locus site sequencing to whole exome sequencing (WES) or whole genome sequencing (WGS), more and more pathogenic genes affecting the occurrence and development of diseases have been discovered. At present, the pathophysiological mechanisms of ALS mainly include abnormal protein aggregation, abnormal DNA or RNA function, changes in cytoskeleton and axon dynamics, autophagy process, lysosome dysfunction, and mitochondrial dysfunction. Exploring the genetic mechanism of ALS has great significance to elucidate its pathophysiological mechanism. This paper reviews the main pathogenic genes, genetic research methods and related pathogenic mechanisms of ALS, reveals the pathogenesis and development of the disease and related pathophysiological mechanisms, and provides new strategies for the treatment of ALS.

Key words: Amyotrophic lateral sclerosis, Motor neuron disease, Genetics, Review

赵倩倩, 李宛真, 唐北沙, 王俊岭. 肌萎缩侧索硬化症遗传学机制研究进展[J]. 中国现代神经疾病杂志, 2023, 23(3): 264-269.

ZHAO Qian-qian, LI Wan-zhen, TANG Bei-sha, WANG Jun-ling. Advances on the genetic mechanism of amyotrophic lateral sclerosis[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2023, 23(3): 264-269.

http://journal11.magtechjournal.com/cjcnn/CN/Y2023/V23/I3/264

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