Role of superoxide dismutases in oxidative damage and neurodegenerative disorders.
In recent years, oxidative stress has been implicated in a variety of degenerative processes, diseases, and syndromes. Some of these include atherosclerosis, myocardial infarction, stroke, and ischemia/reperfusion injury; chronic and acute inflammatory conditions such as wound healing; central nervous system disorders such as forms of familial amyotrophic lateral sclerosis (ALS) and glutathione peroxidase-linked adolescent seizures; Parkinson's disease and Alzheimer's dementia; and a variety of other age-related disorders. Among the various biochemical events associated with these conditions, emerging evidence suggests the formation of superoxide anion and expression/activity of its endogenous scavenger, superoxide dismutase (SOD), as a common denominator. This review summarizes the function of SOD under normal physiological conditions as well as its role in the cellular and molecular mechanisms underlying oxidative tissue damage and neurological abnormalities. Experimental evidence from laboratory animals that either overexpress (transgenics) or are deficient (knockouts) in antioxidant enzyme/protein levels and the genetic SOD mutations observed in some familial cases of ALS are also discussed.
Maier
Carolina M
CM
Department of Neurosurgery, Department of Neurology and Neurological Sciences, Program in Neurosciences, Stanford University School of Medicine, Stanford, California, USA. chile@stanford.edu
Chan
Pak H
PH
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000201:enzymology; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology; D000818:Animals; D030801:Animals, Genetically Modified; D001930:Brain Injuries / Q000201:enzymology; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology; D007249:Inflammation / Q000201:enzymology; D007527:Isoenzymes; D051379:Mice; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000201:enzymology*; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000201:enzymology; D020521:Stroke / Q000201:enzymology; D013482:Superoxide Dismutase / Q000378:metabolism*
D007527:Isoenzymes; D013482:Superoxide Dismutase