p38 kinase is activated in the Alzheimer's disease brain.
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.
Hensley
K
K
Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Floyd
R A
RA
Zheng
N Y
NY
Nael
R
R
Robinson
K A
KA
Nguyen
X
X
Pye
Q N
QN
Stewart
C A
CA
Geddes
J
J
Markesbery
W R
WR
Patel
E
E
Johnson
G V
GV
Bing
G
G
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
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