The complex molecular biology of Amyotrophic Lateral Sclerosis (ALS)

Rachel L. Redler, Nikolay Dokholyan

Research output: Chapter in Book/Report/Conference proceedingChapter

90 Citations (Scopus)

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 - Jan 1 2012

Publication series

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

Fingerprint

Amyotrophic Lateral Sclerosis
Molecular Biology
Axonal Transport
Poisons
Nerve Growth Factors
Motor Neurons
Protein Transport
Pathologic Processes
Post Translational Protein Processing
Paralysis
Neurodegenerative Diseases
Quality Control
Glutamic Acid
Cause of Death
Antioxidants
RNA
Pathology
Calcium
Mutation
Enzymes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

Cite this

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

The complex molecular biology of Amyotrophic Lateral Sclerosis (ALS). / Redler, Rachel L.; Dokholyan, Nikolay.

Progress in Molecular Biology and Translational Science. Elsevier B.V., 2012. p. 215-262 (Progress in Molecular Biology and Translational Science; Vol. 107).

Research output: Chapter in Book/Report/Conference proceedingChapter

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