KMS Chongqing Institute of Green and Intelligent Technology, CAS
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 |
DOI | 10.3233/JAD-200995 |
发表期刊 | JOURNAL OF ALZHEIMERS DISEASE |
ISSN | 1387-2877 |
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 |