Oxidative stress and neurotoxicity.
There is increasing awareness of the ubiquitous role of oxidative stress in neurodegenerative disease states. A continuing challenge is to be able to distinguish between oxidative changes that occur early in the disease from those that are secondary manifestations of neuronal degeneration. This perspective highlights the role of oxidative stress in Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and multiple sclerosis, neurodegenerative and neuroinflammatory disorders where there is evidence for a primary contribution of oxidative stress in neuronal death, as opposed to other diseases where oxidative stress more likely plays a secondary or by-stander role. We begin with a brief review of the biochemistry of oxidative stress as it relates to mechanisms that lead to cell death, and why the central nervous system is particularly susceptible to such mechanisms. Following a review of oxidative stress involvement in individual disease states, some conclusions are provided as to what further research should hope to accomplish in the field.
Sayre
Lawrence M
LM
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA. LMS3@case.edu
Perry
George
G
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology