Mutant Cu,Zn superoxide dismutase in motor neuron disease

Cu,Zn superoxide dismutase (Cu,Zn SOD) is one of several anti-oxidant enzym es which defend the cell against damage by oxygen free radicals. Mutations of the SOD1 gene encoding Cu,Zn SOD are found familial amyotrophic lateral sclerosis, a progressive and fatal paralytic disease which is caused by the death of motor neurons in cortex, brainstem and spinal cord. The disease c an be reproduced in transgenic mice by expression of mutant human Cu,Zn SOD . Recent studies both in vitro and in vivo suggest that the effect of mutat ion is to enhance the generation of oxygen radicals by the mutant enzyme. T hus, mutation converts a protective, antioxidant enzyme into a destructive pro-oxidant form which catalyzes free radical damage to which motor neurons are uniquely vulnerable.