(−)-Epigallocatechin-3-gallate ameliorates learning and memory deficits by adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice
Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is a is a polyphenol, and the most abundant catechin in green tea. EGCG has been found to possess potent iron chelating, antioxidant, anti-inflammatory and anti-oncogenic activities. Previous studies have reported that EGCG treatment significantly reduced Aβ generation in human-derived neuroblastoma (SH-SY5Y) cell line, in murine neuron-like cells (N2a) transfected with human “Swedish” mutant APP, and in primary neurons derived from Swedish mutant APP-overexpressing mice (TgAPPsw line 2576). In addition, EGCG has been reported to markedly improve the cognitive deficits, APP processing, and Tau pathology in D-gal-induced AD mice, TgAPPsw line 2576 transgenic mice and PS2 transgenic mice. Taken together these studies suggest that that EGCG treatment is neuroprotective in some cell and animal models of Alzheimer’s disease (AD).
The goal of this study is to examine, the neuroprotective effects of EGCG on neurodegenerative pathology and behavioral deficits exhibited by APP/PS1 transgenic mice. The data found that EGCG treatment dramatically ameliorated the cognitive impairments, reduced the over expression of Aβ(1–40) and amyloid precursor protein (APP), and inhibited the neuronal apoptosis in the APP/PS1 mice. EGCG treatment reduced the number of Aβ and inhibited neuronal apoptosis oin the hippocampus. Furthermore, EGCG treatment enhanced the relative expression level of NGF by increasing the NGF/pro-NGF ratio in the mice. EGCG was also found to activate TrkA signaling by increasing the phosphorylation of TrkA following the increased phosphorylation of c-Raf, ERK1/2, and cAMP response element-binding protein (CREB). Based on these data the authors suggest that EGCG is a potential therapeutic agent to provide beneficial effects on aging and AD.