CSpace
Ameliorating Ribosylation-Induced Amyloid-beta Pathology by Berberine via Inhibiting mTOR/p70S6K Signaling
Wang, Yang-Yang1,2; Yan, Qian3; Huang, Zhen-Ting1,2; Zou, Qian1,2; Li, Jing1,2; Yuan, Ming-Hao1,2; Wu, Liang-Qi3,4; Cai, Zhi-You1,2
2021
摘要Background: Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer's disease (AD), inhibiting amyloid-beta (A beta) production and promoting A beta clearance. Advanced glycation end products (AGEs) promote A beta aggregation and tau hyperphosphorylation. The activation of mTOR signaling occurring at the early stage of AD has a prominent impact on the A beta production. This work focused on whether BBR regulates the production and clearance of ribosylation-induced A beta pathology via inhibiting mTOR signaling. Objective: To explore whether BBR ameliorates ribosylation-induced A beta pathology in APP/PS1 mice. Methods: Western blot and immunofluorescence staining were used to detect the related proteins of the mammalian target of Rapamycin (mTOR) signaling pathway and autophagy, as well as the related kinases of A beta generation and clearance. Tissue sections and Immunofluorescence staining were used to observe A beta(42) in APP/PS1 mice hippocampal. Morris water maze test was used to measure the spatial learning and memory of APP/PS1 mice. Results: BBR improves spatial learning and memory of APP/PS1 mice. BBR limits the activation of mTOR/p70S6K signaling pathway and enhances autophagy process. BBR reduces the activity of BACE1 and y-secretase induced by D-ribose, and enhances A beta-degrading enzymes and Neprilysin, and inhibits the expression of A beta in APP/PS1 mice. Conclusion: BBR ameliorates ribosylation-induced A beta pathology via inhibiting mTOR/p70S6K signaling and improves spatial learning and memory of the APP/PS1 mice.
关键词AGEs Alzheimer's disease amyloid-beta autophagy berberine mTOR
DOI10.3233/JAD-200995
发表期刊JOURNAL OF ALZHEIMERS DISEASE
ISSN1387-2877
卷号79期号:2页码:833-844
通讯作者Wu, Liang-Qi(wulqi@ucas.ac.cn) ; Cai, Zhi-You(caizhiyou@ucas.ac.cn)
收录类别SCI
WOS记录号WOS:000611560100029
语种英语