Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis
Article first published online: 18 NOV 2002
Journal of Neurochemistry
Volume 69, Issue 5, pages 2064–2074, November 1997
How to Cite
Ferrante, R. J., Browne, S. E., Shinobu, L. A., Bowling, A. C., Baik, M. J., MacGarvey, U., Kowall, N. W., Brown, R. H. and Beal, M. F. (1997), Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis. Journal of Neurochemistry, 69: 2064–2074. doi: 10.1046/j.1471-4159.1997.69052064.x
- Issue published online: 18 NOV 2002
- Article first published online: 18 NOV 2002
- Received May 13, 1997; revised manuscript received June 26, 1997; accepted June 27, 1997.
- Amyotrophic lateral sclerosis;
- Free radicals;
- Oxidative damage;
- Superoxide dismutase
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.