Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci

Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, University of South Florida, Tampa, Florida 33613, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2005; 25(38):8807-14. DOI: 10.1523/JNEUROSCI.1521-05.2005
Source: PubMed


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.

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    • "In fact, EGCG can easily cross the BBB and reach the brain parenchyma [124]. Besides, long term administration was shown to improve spatial cognition and learning ability in rats [125] and to reduce cerebral amyloidosis in AD transgenic mice [126]. Moreover, the consumption of EGCG inhibits OS-induced neuronal degeneration and cell death in pre-and post-traumatic brain injury [127]. "
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    • "Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by the deposition of í µí»½amyloid (Aí µí»½) peptides as senile plaques in the brain. EGCG has been proven to reduce Aí µí»½ generation [38]. Moreover, many key targets in Alzheimer's disease pathway can also be mediated by the GTPs. "
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    • "Studies have shown that EGCG reduces amyloid-␤ (A␤) levels [9] [10] [11], and in so doing can decrease A␤-induced mitochondrial dysfunction [12] and memory impairment [9]. EGCG has been investigated in the Tg2576 AD mouse model [13], where it was shown to decrease A␤ levels by promoting increased amyloid-␤ protein precursor (A␤PP) cleavage through activation of ADAM10, an ␣-secretase [14]. Additionally, oral administration of EGCG (50 mg/kg/daily for 6 months) in these mice resulted in decreased levels of soluble and insoluble oligomeric A␤ species, as well as amelioration of spatial learning deficits, as shown by improved acquisition in the radial-arm water maze [15]. "
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