The Molecular Mechanisms and Therapeutic Approaches of Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS) is a chronic, progressive neurodegenerative disease that primarily damages upper and lower motor neurons. This leads to muscle weakness, atrophy, and ultimately impairs motor function. Currently, there is no cure. Its pathogenesis is closely linked to genetic and environmental factors, as well as their interactions. Approximately 10% of cases are caused by gene mutations. The main pathogenic genes include C9orf72, SOD1, FUS, and TARDBP, which damage neurons through mechanisms such as RNA metabolism disorders and toxic protein aggregation. Among environmental factors, toxin exposure, pesticide contact, and unhealthy lifestyle habits can accelerate neurodegeneration via oxidative stress and mitochondrial damage. In terms of treatment, current strategies mainly focus on targeted interventions. Drugs like tofersen, which target SOD1 mutations, are already in clinical use. However, treatments for genetic abnormalities such as C9orf72, FUS, and TARDBP remain in the research phase. Additionally, chelating agents can be used to remove heavy metals, and anti-inflammatory drugs to block the damage process in response to environment-related pathogenic factors. This article systematically reviews the genetic and environmental risk factors, core molecular mechanisms, and targeted therapeutic strategies for ALS, aiming to provide a theoretical reference for early intervention and the development of novel treatment options for this disease.