Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. Development: This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironnnent) may be involved in motor neurons degeneration. Conclusions: ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established. (C) 2016 Sociedad Espanola de Neurologia. Published by Elsevier Espana, S.L.U.