Oxidants and the central nervous system: some fundamental questions. Is oxidant damage relevant to Parkinson's disease, Alzheimer's disease, traumatic injury or stroke?
Radicals are species containing one or more unpaired electrons. The oxygen radical superoxide (O2-) and the non-radical oxidant hydrogen peroxide (H2O2) are produced during normal metabolism and perform several useful functions. Excessive production of O2- and H2O2 can result in tissue damage, which often involves generation of highly-reactive hydroxyl radical (.OH) and other oxidants in the presence of "catalytic" iron ions. A major form of antioxidant defence is the storage and transport of iron ions in forms that will not catalyze formation of reactive radicals. Tissue injury, eg. by ischaemia or trauma, can cause increased iron availability and accelerate free radical reactions. This may be especially important in the brain, since areas of this organ are rich in iron and cerebrospinal fluid cannot bind released iron ions. Oxidant stress upon nervous tissue can produce damage by several interacting mechanisms, including rises in intracellular free Ca2+ and, possibly, release of excitatory amino acids. Recent suggestions that iron-dependent free radical reactions are involved in the neurotoxicity of aluminium and in damage to the substantia nigra in Parkinson's disease are reviewed. Finally, the nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of iron ions may be more generally-useful protective agents than chain-breaking antioxidants.
Halliwell
B
B
Department of Biochemistry, King's College, University of London, U.K.
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D001930:Brain Injuries / Q000209:etiology* / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000209:etiology* / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D010100:Oxygen / Q000378:metabolism / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism
D005609:Free Radicals; D010100:Oxygen