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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: 6.75). 10/2005; 25(38):8807-14. DOI: 10.1523/JNEUROSCI.1521-05.2005
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ABSTRACT 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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    ABSTRACT: Diabetes mellitus (DM) is a metabolic disease that is rapidly increasing and has become a major public health problem. Type 2 DM (T2DM) is the most common type, accounting for up to 90-95% of the new diagnosed DM cases. The brain is very susceptible to glucose fluctuations and hyperglycemia-induced oxidative stress (OS). It is well known that DM and the risk of developing neurodegenerative diseases are associated. Tea, Camellia sinensis L., is one of the most consumed beverages. It contains several phytochemicals, such as polyphenols, methylxanthines (mainly caffeine) and L-theanine that are often reported to be responsible for tea’s health benefits, including in brain. Tea phytochemicals have been reported to be responsible for tea’s significant antidiabetic and neuroprotective properties and antioxidant potential. Epidemiological studies have shown that regular consumption of tea has positive effects on DM-caused complications and protects the brain against oxidative damage, contributing to an improvement of the cognitive function. Among the several reported benefits of tea consumption, those related with neurodegenerative diseases are of great interest. Herein, we discuss the potential beneficial effects of tea consumption and tea phytochemicals on DM and how their action can counteract the severe brain damage induced by this disease.
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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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    ABSTRACT: During the past decades, a number of studies have demonstrated multiple beneficial health effects of green tea. Polyphenolics are the most biologically active components of green tea. Many targets can be targeted or affected by polyphenolics. In this study, we excavated all of the targets of green tea polyphenolics (GTPs) though literature mining and target calculation and analyzed the multiple pharmacology actions of green tea comprehensively through a network pharmacology approach. In the end, a total of 200 Homo sapiens targets were identified for fifteen GTPs. These targets were classified into six groups according to their related disease, which included cancer, diabetes, neurodegenerative disease, cardiovascular disease, muscular disease, and inflammation. Moreover, these targets mapped into 143 KEGG pathways, 26 of which were more enriched, as determined though pathway enrichment analysis and target-pathway network analysis. Among the identified pathways, 20 pathways were selected for analyzing the mechanisms of green tea in these diseases. Overall, this study systematically illustrated the mechanisms of the pleiotropic activity of green tea by analyzing the corresponding "drug-target-pathway-disease" interaction network.
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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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