Early decrease of redox factor-1 in spinal motor neurons of presymptomatic transgenic mice with a mutant SOD1 gene.

Oxidative stress has been proposed to play a pivotal role in pathogenesis of both sporadic and familial amyotrophic lateral sclerosis (ALS). Expression of DNA repair enzyme redox factor-1 (Ref-1) protein was examined in the spinal cord of transgenic mice with an ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) gene. Immunoblotting and immunocytochemical analyses showed that the most spinal motor neurons lost the immunoreactivity for Ref-1 in the early presymptomatic stage that preceded significant loss of the neurons. The present result suggests that an early impairment of DNA repair in the spinal motor neurons may account for the mutant SOD1-mediated motor neuronal death in this model.