Activation of NADPH oxidase in Alzheimer's disease brains.
The present study is the first to show that superoxide (O(-)(2)) forming NADPH oxidase is activated in Alzheimer's disease (AD) brains by demonstrating the marked translocation of the cytosolic factors p47-phox and p67-phox to the membrane. In conjunction with a recent in vitro study showing that amyloid beta activates O(-)(2) forming NADPH oxidase in microglia, where these phox proteins are localized in this study, the present results suggest that, in AD, NADPH oxidase is activated in microglia, resulting in the formation of reactive oxygen species which can be toxic to neighboring neurons in AD.
Shimohama
S
S
Department of Neurology, Kyoto University, Kyoto, 606-8507, Japan.
Tanino
H
H
Kawakami
N
N
Okamura
N
N
Kodama
H
H
Yamaguchi
T
T
Hayakawa
T
T
Nunomura
A
A
Chiba
S
S
Perry
G
G
Smith
M A
MA
Fujimoto
S
S
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D010750:Phosphoproteins; D017382:Reactive Oxygen Species; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1