Metal ions and oxidative protein modification in neurological disease.
This review highlights the role of oxidative stress and imbalances in metal ion homeostasis in the neurodegenerative diseases Alzheimer's disease and Parkinson's disease and in the progressive demyelinating disease multiple sclerosis. The chemistry and biochemistry of oxidative stress-induced protein damage are first described, followed by the evidence for a pathological role of oxidative stress in these disease states. It is tempting to speculate that free radical oxygen chemistry contributes to pathogenesis in all these conditions, though it is as yet undetermined what types of oxidative changes occur early in the disease, and what types are secondary manifestations of neuronal degeneration.
Sayre
Lawrence M
LM
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA. lms3@po.cwru.edu
Moreira
Paula I
PI
Smith
Mark A
MA
Perry
George
G
D000447:Aldehydes / Q000494:pharmacology; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D005609:Free Radicals / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism / Q000494:pharmacology; D008670:Metals / Q000009:adverse effects* / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000209:etiology / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D000447:Aldehydes; D003432:Cross-Linking Reagents; D005609:Free Radicals; D017127:Glycation End Products, Advanced; D008670:Metals; D011506:Proteins; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal