Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease primarily affecting motor neurons, leading to progressive muscle atrophy and paralysis. This review explores the role of Schwann cells in ALS pathogenesis, highlighting their influence on disease progression through mechanisms involving demyelination, neuroinflammation, and impaired synaptic function. While Schwann cells have been traditionally viewed as peripheral supportive cells, especially in motor neuron disease, recent evidence indicates that they play a significant role in ALS by impacting motor neuron survival and plasticity, influencing inflammatory responses, and altering myelination processes. Furthermore, advancements in understanding Schwann cell pathology in ALS combined with lessons learned from studying Charcot-Marie-Tooth disease Type 1 (CMT1) suggest potential therapeutic strategies targeting these cells may support nerve repair and slow disease progression. Overall, this review aims to provide comprehensive insights into Schwann cell classification, physiology, and function, underscoring the critical pathological contributions of Schwann cells in ALS and suggests new avenues for targeted therapeutic interventions aimed at modulating Schwann cell function in ALS.
Keywords: ALS; CMT1; NMJ; Schwann cell; myelin; satellite glial cells; terminal Schwann cells.