肌萎缩侧索硬化症遗传学机制研究进展

Advances on the genetic mechanism of amyotrophic lateral sclerosis

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。

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.