RT Journal Article
SR Electronic
T1 Green Tea Epigallocatechin-3-Gallate (EGCG) Modulates Amyloid Precursor Protein Cleavage and Reduces Cerebral Amyloidosis in Alzheimer Transgenic Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8807
OP 8814
DO 10.1523/JNEUROSCI.1521-05.2005
VO 25
IS 38
A1 Rezai-Zadeh, Kavon
A1 Shytle, Doug
A1 Sun, Nan
A1 Mori, Takashi
A1 Hou, Huayan
A1 Jeanniton, Deborah
A1 Ehrhart, Jared
A1 Townsend, Kirk
A1 Zeng, Jin
A1 Morgan, David
A1 Hardy, John
A1 Town, Terrence
A1 Tan, Jun
YR 2005
UL http://www.jneurosci.org/content/25/38/8807.abstract
AB Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by deposition of β-amyloid (Aβ) 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 Aβ 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 α-C-terminal fragment of APP and elevates the N-terminal APP cleavage product, soluble APP-α. These cleavage events are associated with elevated α-secretase activity and enhanced hydrolysis of tumor necrosis factor α-converting enzyme, a primary candidate α-secretase. As a validation of these findings in vivo, we treated Tg APPsw transgenic mice overproducing Aβ with EGCG and found decreased Aβ levels and plaques associated with promotion of the nonamyloidogenic α-secretase proteolytic pathway. These data raise the possibility that EGCG dietary supplementation may provide effective prophylaxis for AD.