EVIDENCE OF REDUCED DNA-REPAIR IN AMYOTROPHIC-LATERAL-SCLEROSIS BRAIN-TISSUE

Oxidative stress is proposed to play a central role in the pathogenesi s of amyotrophic lateral sclerosis (ALS). Anti-oxidant enzymes and DNA repair proteins are two major mechanisms by which cells counteract th e deleterious effects of reactive oxygen species (ROS). Neurons may be particularly vulnerable to ROS-induced oxidative DNA damage; this is repaired by the base-excision repair (BER) pathway. Frontal cortical l evels and activity of the pivotal BER protein apurinic/apyrimidinic en donuclease (APE) were determined in 11 patients with sporadic ALS and six age-matched control subjects. APE levels (p < 0.003) and activity (p < 0.000007) were significantly lower in ALS subjects than in contro ls. These findings suggest that ALS brain tissue is inefficient in rep airing oxidative DNA damage.