Amyotrophic lateral sclerosis: Neural repair strategies based on multi-target synchronous interventions

Abstract Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease that targets motor neurons in the cerebral cortex, medulla oblongata, and spinal cord. This review focuses on the current concepts in the aetiopathogenesis and diagnosis of amyotrophic lateral sclerosis, aiming to explore potential neural repair strategies (curative and/or progression-retarding therapeutics). Recent studies have highlighted that the complex pathogenesis of amyotrophic lateral sclerosis is related to its multifactorial aetiology, including proteostasis disruption, impaired RNA metabolism and DNA repair, cytoskeletal and axonal transport defects, excitotoxicity, neuroinflammation, mitochondrial dysfunction, oligodendrocyte dysfunction, nucleocytoplasmic transport deficits, lipid dyshomeostasis, and autophagy. Several approved drugs are currently used to treat patients with amyotrophic lateral sclerosis; however, their curative efficacy is limited. Thus, the search for effective therapeutic strategies for amyotrophic lateral sclerosis requires a comprehensive understanding of its pathogenesis. Current evidence indicates that a single drug cannot provide a satisfactory therapeutic effect. Additionally, multiple pathophysiological processes and related targets are involved in the pathogenesis of amyotrophic lateral sclerosis. Therefore, research on multi-target synchronous interventions may be the path forward for discovering and developing potential neural repair strategies.