Encyclopedia of Metalloproteins

2013 Edition
| Editors: Robert H. Kretsinger, Vladimir N. Uversky, Eugene A. Permyakov

Copper-Zinc Superoxide Dismutase and Lou Gehrig’s Disease

  • Herman Louis Lelie
  • Joan Selverstone Valentine
Reference work entry
DOI: https://doi.org/10.1007/978-1-4614-1533-6_103

Synonyms

Definition

Copper-zinc superoxide dismutase (SOD1) is an antioxidant metalloenzyme that is present throughout the body. It catalyzes the conversion of two molecules of superoxide into hydrogen peroxide and molecular oxygen in a reaction that involves alternate oxidation and reduction of the active site copper ion. Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons, leading inevitably to paralysis and death, usually within 3–5 years. Onset of disease is usually after age 50, and there is no cure. Most cases have no known genetic component, but in a small fraction of cases, ALS is caused by point mutations in SOD1. This linkage of SOD1 and ALS, first published in 1993, provided the first experimental route to...

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References

  1. Bruijn LI, Miller TM et al (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27(1):723–749CrossRefPubMedGoogle Scholar
  2. Chattopadhyay M, Valentine JS (2009) Aggregation of copper-zinc superoxide dismutase in familial and sporadic ALS. Antioxid Redox Signal 11(7):1603–1614CrossRefPubMedGoogle Scholar
  3. Cleveland DW, Rothstein JD (2001) From charcot to lou gehrig: deciphering selective motor neuron death in als. Nat Rev Neurosci 2(11):806–819CrossRefPubMedGoogle Scholar
  4. Lelie HL, Borchelt DR et al (2011) Metal toxicity and metallostasis in amyotrophic lateral sclerosis. In: Milardi D, Rizzarelli E, Milardi D, Rizzarelli E (eds) Neurodegeneration: metallostasis and proteostasis (Rsc drug discovery). Royal Society of Chemistry, Cambridge, IN PRESSGoogle Scholar
  5. Shaw BF, Valentine JS (2007) How do ALS-associated mutations in superoxide dismutase 1 promote aggregation of the protein? Trends Biochem Sci 32(2):78–85CrossRefPubMedGoogle Scholar
  6. Turner BJ, Talbot K (2008) Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Prog Neurobiol 85(1):94–134CrossRefPubMedGoogle Scholar
  7. Valentine JS, Hart PJ (2003) Misfolded CuZnSOD and amyotrophic lateral sclerosis. Proc Natl Acad Sci 100(7):3617–3622CrossRefPubMedGoogle Scholar
  8. Valentine JS, Doucette PA et al (2005) Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis. Annu Rev Biochem 74(1):563–593CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Herman Louis Lelie
    • 1
  • Joan Selverstone Valentine
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of CaliforniaLos AngelesUSA