Evidence of reduced DNA repair in amyotrophic lateral sclerosis brain tissue.
Oxidative stress is proposed to play a central role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Anti-oxidant enzymes and DNA repair proteins are two major mechanisms by which cells counteract the 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 levels and activity of the pivotal BER protein apurinic/apyrimidinic endonuclease (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 controls. These findings suggest that ALS brain tissue is inefficient in repairing oxidative DNA damage.
Kisby
G E
GE
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201, USA.
Milne
J
J
Sweatt
C
C
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005260:Female; D006801:Humans; D008190:Lyases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D043223:Deoxyribonuclease IV (Phage T4-Induced); D008190:Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase