• Mingyan Liu, Fujun Chen, Lei Sha, Shuang Wang, Lin Tao, Lutian Yao, Miao He, Zhimin Yao, Hang Liu, Zheng Zhu, Zhenjie Zhang, Zhihong Zheng, Xianzheng Sha, and Minjie Wei.
• Department of Pharmacology, School of Pharmaceutical Sciences, China Medical University, No.92 Bei'er Road, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.
• Mol. Neurobiol. 2014 Jun 1;49(3):1350-63.

AbstractAlzheimer's disease (AD) is pathologically characterized by deposition of β-amyloid (Aβ) peptides, which closely correlates with the balance of nerve growth factor (NGF)-related TrkA/p75NTR signaling. (-)-Epigallocatechin-3-gallate (EGCG) is used for prevention and treatment of many neurodegenerative diseases, including AD. However, whether the neuroprotective effects of EGCG treatment were via modulating the balance of TrkA/p75NTR signaling was still unknown. In this study, we found that EGCG treatment (2 mg·kg(-1)·day(-1)) dramatically ameliorated the cognitive impairments, reduced the overexpressions of Aβ(1-40) and amyloid precursor protein (APP), and inhibited the neuronal apoptosis in the APP/PS1 mice. Interestingly, the EGCG treatment enhanced the relative expression level of NGF by increasing the NGF/proNGF ratio in the APP/PS1 mice. Moreover, after EGCG treatment, TrkA signaling was activated by increasing the phosphorylation of TrkA following the increased phosphorylation of c-Raf, ERK1/2, and cAMP response element-binding protein (CREB), simultaneously the p75NTR signaling was significantly inhibited by decreasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression, so that the Aβ deposits and neuronal apoptosis in the hippocampus were inhibited.

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