Role of SOD1 on the Etiology, Pathophysiology and Therapeutic approaches for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a grievous neurodegenerative disease whose survival is limited to only a few years. It is an intractable disease that causes respiratory failure leading to mortality. Several theories have been proposed, involving genetic factors, molecular dysfunctions, and cellular abnormalities. Growing evidence has linked oxidative stress (OS) and genetic mutations to disease progression, particularly mutations in the superoxide dismutase 1 (SOD1) gene. SOD1 plays a key role in regulating reactive oxygen species (ROS) generated by the electron transport chain and promotes the activation of genes that defend against oxidative stress. This review provides a comprehensive overview of ALS etiology, highlighting the molecular and cellular mechanisms implicated in its pathogenesis besides the treatment approaches for ALS and the physiological role of SOD1 in cellular defense against oxidative stress and its regulation within different cellular compartments. Currently, multiple FDA-approved therapies are available for ALS which are designed either to partially address the effects of the SOD1 mutation or to inhibit cellular and neurological pathways involved in motor neuron degeneration. By integrating insights from genetics, molecular biology, and environmental studies, this review aims to deepen the understanding of SOD1-related mechanisms in ALS and identify potential avenues for future therapeutic intervention.