Molecular and Cellular Mechanisms Affected in ALS

• Published in: Journal of personalized medicine Vol. 10; no. 3; p. 101
• Main Authors: Gall, Laura Le, Anakor, Ekene, Connolly, Owen, Vijayakumar, Udaya Geetha, Duddy, William J, Duguez, Stephanie
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-09-2020; MDPI
• Subjects: Amyotrophic lateral sclerosis; Antioxidants; Axonal transport; Deoxyribonucleic acid; Development and progression; DNA; DNA damage; Excitotoxicity; Genes; Genetic aspects; Homeostasis; Hypotheses; Kinases; Mitochondria; Molecular modelling; Morphology; Motor neurons; Mutation; Neurons; Oxidative stress; Pathology; Precision medicine; Protein transport; Protein turnover; Proteins; Review; Ribonucleic acid; RNA; Spinal cord; Toxicity; United Kingdom
• ISSN: 2075-4426; 2075-4426
• DOI: 10.3390/jpm10030101

Amyotrophic lateral sclerosis (ALS) is a terminal late-onset condition characterized by the loss of upper and lower motor neurons. Mutations in more than 30 genes are associated to the disease, but these explain only ~20% of cases. The molecular functions of these genes implicate a wide range of cellular processes in ALS pathology, a cohesive understanding of which may provide clues to common molecular mechanisms across both familial (inherited) and sporadic cases and could be key to the development of effective therapeutic approaches. Here, the different pathways that have been investigated in ALS are summarized, discussing in detail: mitochondrial dysfunction, oxidative stress, axonal transport dysregulation, glutamate excitotoxicity, endosomal and vesicular transport impairment, impaired protein homeostasis, and aberrant RNA metabolism. This review considers the mechanistic roles of ALS-associated genes in pathology, viewed through the prism of shared molecular pathways.