Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis


Address correspondence and reprint requests to Dr. M. Flint Beal at Neurology/WRN 408, Massachusetts General Hospital, 32 Fruit Street, Boston, MA 02114, U.S.A.


Abstract: Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined markers of oxidative damage to protein, lipids, and DNA in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Protein carbonyl and nuclear DNA 8-hydroxy-2′-deoxyguanosine (OH8dG) levels were increased in SALS motor cortex but not in FALS patients. Malondialdehyde levels showed no significant changes. Immunohistochemical studies showed increased neuronal staining for hemeoxygenase-1, malondialdehyde-modified protein, and OH8dG in both SALS and FALS spinal cord. These studies therefore provide further evidence that oxidative damage may play a role in the pathogenesis of neuronal degeneration in both SALS and FALS.

Abbreviations used: ALS, amyotrophic lateral sclerosis; dG, deoxyguanosine; DLBD, diffuse Lewy body disease; FALS, familial amyotrophic lateral sclerosis; nDNA, nuclear DNA; OH8dG, 8-hydroxy-2′-deoxyguanosine; PBS, phosphate-buffered saline; PSP, progressive supranuclear palsy; SALS, sporadic amyotrophic lateral sclerosis; SOD1, Cu/Zn superoxide dismutase.