Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis
- PMID: 8560268
- DOI: 10.1126/science.271.5248.515
Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis
Abstract
A subset of individuals with familial amyotrophic lateral sclerosis (FALS) possesses dominantly inherited mutations in the gene that encodes copper-zinc superoxide dismutase (CuZnSOD). A4V and G93A, two of the mutant enzymes associated with FALS, were shown to catalyze the oxidation of a model substrate (spin trap 5,5'-dimethyl-1-pyrroline N-oxide) by hydrogen peroxide at a higher rate than that seen with the wild-type enzyme. Catalysis of this reaction by A4V and G93A was more sensitive to inhibition by the copper chelators diethyldithiocarbamate and penicillamine than was catalysis by wild-type CuZnSOD. The same two chelators reversed the apoptosis-inducing effect of mutant enzymes expressed in a neural cell line. These results suggest that oxidative reactions catalyzed by mutant CuZnSOD enzymes initiate the neuropathologic changes in FALS.
Comment in
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Mutant enzyme provides new insights into the cause of ALS.Science. 1996 Jan 26;271(5248):446-7. doi: 10.1126/science.271.5248.446. Science. 1996. PMID: 8560253 No abstract available.
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