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J Nutr. 2009 Oct;139(10):1987-93. Epub 2009 Aug 5.
Green tea (-)-epigallocatechin-3-gallate inhibits beta-amyloid-induced
cognitive dysfunction through modification of secretase activity via
inhibition of ERK and NF-kappaB pathways in mice.
Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT.
College of Pharmacy, Chungbuk National University 12, Gaesin-dong,
Heungduk-gu, Cheongju, Chungbuk 361-763, Korea.
Alzheimer's disease (AD) is characterized by the extracellular
deposition of beta-amyloid peptide (Abeta) in cerebral plaques. Abeta is
derived from the beta-amyloid precursor protein (APP) by the enzymes
alpha-, beta- and gamma-secretase. Compounds that enhance
alpha-secretase, but inhibit beta- or gamma-secretase activity, have
therapeutic potential in the treatment of AD. Green tea, or its major
polyphenolic compound, has been shown to have neuroprotective effects.
In this study, we investigated the possible effects of
(-)-epigallocatechin-3-gallate (EGCG) on memory dysfunction caused by
Abeta through the change of Abeta-induced secretase activities. Mice
were pretreated with EGCG (1.5 or 3 mg/kg body weight in drinking water)
for 3 wk before intracerebroventricular administration of 0.5 microg
Abeta(1-42). EGCG dose-dependently reduced the Abeta(1-42)-induced
memory dysfunction, which was evaluated using passive avoidance and
water maze tests. Abeta(1-42) induced a decrease in brain
alpha-secretase and increases in both brain beta- and gamma-secretase
activities, which were reduced by EGCG. In the cortex and the
hippocampus, expression of the metabolic products of the beta- and
gamma-secretases from APP, C99, and Abeta also were dose-dependently
suppressed by EGCG. Paralleled with the suppression of beta- and
gamma-secretases by EGCG, we found that EGCG inhibited the activation of
extracellular signal-regulated kinase and nuclear transcription
factor-kappaB in the Abeta(1-42)-injected mouse brains. In addition,
EGCG inhibited Abeta(1-42)-induced apoptotic neuronal cell death in the
brain. To further test the ability of EGCG to affect memory, EGCG (3
mg/kg body weight) was administered in drinking water for 1 wk to
genetically developed preseniline 2 (PS2) mutant AD mice. Compared with
untreated mutant PS2 AD mice, treatment with EGCG enhanced memory
function and brain alpha-secretase activity but reduced brain beta- and
gamma-secretase activities as well as Abeta levels. Moreover, EGCG
inhibited the fibrillization of Abeta in vitro with a half maximal
inhibitory concentration of 7.5 mg/L. These studies suggest that EGCG
may be a beneficial agent in the prevention of development or
progression of AD.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19656855 |
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