title: Superoxide dismutase and the death of motoneurons in ALS.
abstract: Amyotrophic lateral sclerosis (ALS) is a lethal disease that is characterized by the relentless death of motoneurons. Mutations to Cu-Zn superoxide dismutase (SOD), though occurring in just 2-3% of individuals with ALS, remain the only proven cause of the disease. These mutations structurally weaken SOD, which indirectly decreases its affinity for Zn. Zn-deficient SOD induces apoptosis in motoneurons through a mechanism involving peroxynitrite. Importantly, Zn-deficient wild-type SOD is just as toxic as Zn-deficient ALS mutant SOD, suggesting that the loss of Zn from wild-type SOD could be involved in the other 98% of cases of ALS. Zn-deficient SOD could therefore be an important therapeutic target in all forms of ALS.
authors.affiliation: Linus Pauling Institute, and Dept of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA. joe.beckman@orst.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Beckman
authors.forename: A G
authors.initials: AG
authors.lastname: Estévez
authors.forename: J P
authors.initials: JP
authors.lastname: Crow
authors.forename: L
authors.initials: L
authors.lastname: Barbeito
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology*; D016923:Cell Death; D006801:Humans; D009046:Motor Neurons / Q000201:enzymology* / Q000473:pathology*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D013482:Superoxide Dismutase