Redox proteomic analysis of carbonylated brain proteins in mild cognitive impairment and early Alzheimer's disease.
Previous studies indicated increased levels of protein oxidation in brain from subjects with Alzheimer's disease (AD), raising the question of whether oxidative damage is a late effect of neurodegeneration or precedes and contributes to the pathogenesis of AD. Hence, in the present study we used a parallel proteomic approach to identify oxidatively modified proteins in inferior parietal lobule (IPL) from subjects with mild cognitive impairment (MCI) and early stage-AD (EAD). By comparing to age-matched controls, we reasoned that such analysis could help in understanding potential mechanisms involved in upstream processes in AD pathogenesis. We have identified four proteins that showed elevated levels of protein carbonyls: carbonic anhydrase II (CA II), heat shock protein 70 (Hsp70), mitogen-activated protein kinase I (MAPKI), and syntaxin binding protein I (SBP1) in MCI IPL. In EAD IPL we identified three proteins: phosphoglycerate mutase 1 (PM1), glial fibrillary acidic protein, and fructose bisphospate aldolase C (FBA-C). Our results imply that some of the common targets of protein carbonylation correlated with AD neuropathology and suggest a possible involvement of protein modifications in the AD progression.
Sultana
Rukhsana
R
Department of Chemistry, University of Kentucky , Lexington, KY, USA.
Perluigi
Marzia
M
Newman
Shelley F
SF
Pierce
William M
WM
Cini
Chiara
C
Coccia
Raffaella
R
Butterfield
D Allan
DA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D010084:Oxidation-Reduction; D050050:Protein Carbonylation / Q000502:physiology*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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