Superoxide dismutase and the death of motoneurons in ALS.
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.
Beckman
J S
JS
Linus Pauling Institute, and Dept of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA. joe.beckman@orst.edu
Estévez
A G
AG
Crow
J P
JP
Barbeito
L
L
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*
D013482:Superoxide Dismutase