Proteomic analysis of oxidatively modified proteins in Alzheimer's disease brain: insights into neurodegeneration.
Identification of oxidized proteins in Alzheimer's disease (AD) brain is hypothesized to lead to new insights into mechanisms of neurodegeneration and synapse loss in this dementing disorder that are associated with oxidative stress. Previous studies had shown increased oxidation of proteins in AD brain, but identifying those particular proteins that were specifically oxidized using standard immunochemical methods is a daunting task when one considers how many proteins there are in brain. To address this issue, proteomics has been used to identify specifically modified proteins in AD brain. This review outlines the nature of proteomics, the proteins identified in AD brain that are specifically oxidatively modified, and provides rational consequences related to neurodegeneration and synapse loss as sequelae to loss of function, due to oxidation and consistent with the known pathological and biochemical alteration in AD brain. The use of proteomics to learn about disease mechanisms is still embryonic, but the emerging techniques of proteomics represent a promising means to elucidate mechanisms of disease at the protein level. There are limitations to proteomics, and these, too, are discussed.
Butterfield
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DA
Department of Chemistry, Center of Membrane Sciences, Sanders-Brown Center on Aging, 121 Chemistry-Physics Building, University of Kentucky, Lexington, KY 40506-0055, USA. dabcns@uky.edu
Castegna
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A
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D020543:Proteome / Q000032:analysis* / Q000502:physiology; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D020543:Proteome