Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by deposition of beta-amyloid (Abeta) peptides as senile plaques in the brain. Recent studies suggest that green tea flavonoids may be used for the prevention and treatment of a variety of neurodegenerative diseases. Here, we report that (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, reduces Abeta generation in both murine neuron-like cells (N2a) transfected with the human "Swedish" mutant amyloid precursor protein (APP) and in primary neurons derived from Swedish mutant APP-overexpressing mice (Tg APPsw line 2576). In concert with these observations, we find that EGCG markedly promotes cleavage of the alpha-C-terminal fragment of APP and elevates the N-terminal APP cleavage product, soluble APP-alpha. These cleavage events are associated with elevated alpha-secretase activity and enhanced hydrolysis of tumor necrosis factor alpha-converting enzyme, a primary candidate alpha-secretase. As a validation of these findings in vivo, we treated Tg APPsw transgenic mice overproducing Abeta with EGCG and found decreased Abeta levels and plaques associated with promotion of the nonamyloidogenic alpha-secretase proteolytic pathway. These data raise the possibility that EGCG dietary supplementation may provide effective prophylaxis for AD.
Rezai-Zadeh
Kavon
K
Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, University of South Florida, Tampa, Florida 33613, USA.
Shytle
Doug
D
Sun
Nan
N
Mori
Takashi
T
Hou
Huayan
H
Jeanniton
Deborah
D
Ehrhart
Jared
J
Townsend
Kirk
K
Zeng
Jin
J
Morgan
David
D
Hardy
John
J
Town
Terrence
T
Tan
Jun
J
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D013662:Tea
D016564:Amyloid beta-Protein Precursor; D005419:Flavonoids; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate