Mutant CuZn superoxide dismutase in motor neuron disease

摘要: CuZn superoxide dismutase (CuZn SOD) is one of several antioxidant enzymes that defend the cell against damage by oxygen free radicals. Mutations SODI gene encoding SOD are found in patients with familial amyotrophic lateral sclerosis (FALS), a progressive and fatal paralytic disease caused death motor neurons cortex, brainstem spinal cord. The can be reproduced transgenic mice expression mutant human SOD. Recent studies both vitro vivo suggest effect mutation to enhance generation radicals enzyme. Thus, converts protective, enzyme into destructive, prooxidant form catalyses radical which selectively vulnerable. neuroprotective agents FALS model show inhibition oxidative mechanisms (copper chelation therapy, dietary antioxidants, coexpression bcl-2) delays onset but does not extend duration. In contrast, glutamatergic or apoptotic (riluzole, gabapentin, an inhibitor caspase-1) has no on extends survival increasing duration symptomatic disease. differentially target processes underlying initiation propagation.