title: (-)-Epigallocatechin-3-gallate ameliorates learning and memory deficits by adjusting the balance of TrkA/p75NTR signaling in APP/PS1 transgenic mice.
abstract: Alzheimer'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.
authors.affiliation: 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.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Liu
authors.forename: Fujun
authors.initials: F
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Sha
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Tao
authors.forename: Lutian
authors.initials: L
authors.lastname: Yao
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yao
authors.forename: Hang
authors.initials: H
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhu
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xianzheng
authors.initials: X
authors.lastname: Sha
authors.forename: Minjie
authors.initials: M
authors.lastname: Wei
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics; D020917:Receptor, trkA / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D002392:Catechin; C045651:epigallocatechin gallate; D020917:Receptor, trkA