Advances on the genetic mechanism of amyotrophic lateral sclerosis

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.

doi：10.3969/j.issn.1672⁃6731.2023.03.017