title: p38 kinase is activated in the Alzheimer's disease brain.
abstract: The p38 mitogen-activated protein kinase is a stress-activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) p38 were detected relative to age-matched normal brain. Intense phospho-p38 immunoreactivity was associated with neuritic plaques, neuropil threads, and neurofibrillary tangle-bearing neurons. The antibody against phosphorylated p38 recognized many of the same structures as an antibody against aberrantly phosphorylated, paired helical filament (PHF) tau, although PHF-positive tau did not cross-react with the phospho-p38 antibody. These findings suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.
authors.affiliation: Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hensley
authors.forename: R A
authors.initials: RA
authors.lastname: Floyd
authors.forename: N Y
authors.initials: NY
authors.lastname: Zheng
authors.forename: R
authors.initials: R
authors.lastname: Nael
authors.forename: K A
authors.initials: KA
authors.lastname: Robinson
authors.forename: X
authors.initials: X
authors.lastname: Nguyen
authors.forename: Q N
authors.initials: QN
authors.lastname: Pye
authors.forename: C A
authors.initials: CA
authors.lastname: Stewart
authors.forename: J
authors.initials: J
authors.lastname: Geddes
authors.forename: W R
authors.initials: WR
authors.lastname: Markesbery
authors.forename: E
authors.initials: E
authors.lastname: Patel
authors.forename: G V
authors.initials: GV
authors.lastname: Johnson
authors.forename: G
authors.initials: G
authors.lastname: Bing
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003429:Cross Reactions; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D012016:Reference Values; D014018:Tissue Distribution; D048051:p38 Mitogen-Activated Protein Kinases; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C085349:PHF-1 monoclonal antibody; D016875:tau Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases