The complex molecular biology of Amyotrophic Lateral Sclerosis (ALS)

Rachel L. Redler, Nikolay V. Dokholyan

Research output: Chapter in Book/Report/Conference proceedingChapter

97 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder that causes selective death of motor neurons followed by paralysis and death. A subset of ALS cases is caused by mutations in the gene for Cu, Zn superoxide dismutase (SOD1), which impart a toxic gain of function to this antioxidant enzyme. This neurotoxic property is widely believed to stem from an increased propensity to misfold and aggregate caused by decreased stability of the native homodimer or a tendency to lose stabilizing posttranslational modifications. Study of the molecular mechanisms of SOD1-related ALS has revealed a complex array of interconnected pathological processes, including glutamate excitotoxicity, dysregulation of neurotrophic factors and axon guidance proteins, axonal transport defects, mitochondrial dysfunction, deficient protein quality control, and aberrant RNA processing. Many of these pathologies are directly exacerbated by misfolded and aggregated SOD1 and/or cytosolic calcium overload, suggesting the primacy of these events in disease etiology and their potential as targets for therapeutic intervention.

Original languageEnglish (US)
Title of host publicationProgress in Molecular Biology and Translational Science
PublisherElsevier B.V.
Pages215-262
Number of pages48
DOIs
StatePublished - 2012

Publication series

NameProgress in Molecular Biology and Translational Science
Volume107
ISSN (Print)1877-1173

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

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    Redler, R. L., & Dokholyan, N. V. (2012). The complex molecular biology of Amyotrophic Lateral Sclerosis (ALS). In Progress in Molecular Biology and Translational Science (pp. 215-262). (Progress in Molecular Biology and Translational Science; Vol. 107). Elsevier B.V.. https://doi.org/10.1016/B978-0-12-385883-2.00002-3