Genetic Modulators in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is known as one of the fatal diseases among the neurodegenerative disorders. It is characterized by the progressive loss of motor neurons in the cortical, spinal cord, and brainstem regions. This neuronal death leads to paralysis and, in later stages, respiratory failure, often resulting in death. The incidence of ALS is relatively low, with around 1–2 people approx. per 100,000 annually and life expectancy for patients diagnosed is very short, about 3–5 years, as the disease progresses rapidly. ALS is categorized into two forms: familial and sporadic (SALS), with SALS being the most common. Almost 90% of cases are diagnosed without any prior family history of ALS whereas in the less frequent cases up to 10% of patients have familial forms (FALS) of ALS that are mostly found inherited in autosomal dominant patterns. The researchers have identified multiple factors contributing to the development of ALS, including defects in the metabolism of RNA and DNA, disturbance in DNA repair mechanism, protein homeostasis dysfunction, damage in nucleocytoplasmic transport, oxidative stress (OS), excitotoxicity, axonal transport alteration, neuroinflammation, mutation, and nonneuronal cells are also responsible for neurodegeneration. Despite the identification of several genetic factors associated with ALS, the specific mechanism underlying the disease progression remain unclear. Currently, the available treatment strategies are only symptomatic. Hence, further research is required to know the exact mechanism of pathogenesis of the disease. This chapter highlights various genetic modulators and other factors affecting ALS, apart from a mutation in SOD1, several other genes are also discussed as causative factors.