Affiliations: [a] Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, China
| [b]
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China
| [c]
Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, China
| [d]
University of Chinese Academy of Sciences, Beijing, China
Correspondence:
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Correspondence to: Liang-Qi Wu, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, No. 266, Fangzheng Avenue, Beibei District, Chongqing, 400714, People’s Republic of China. Tel.: +86 23 65935555; Fax: +86 23 65935000; E-mail: [email protected]. and Zhi-You Cai, Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, No. 312 Zhongshan First Road, Yuzhong District, Chongqing, 400013, People’s Republic of China. Tel.: +86 23 63515796; Fax: +86 23 63515796; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Background:Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer’s disease (AD), inhibiting amyloid-β (Aβ) production and promoting Aβ clearance. Advanced glycation end products (AGEs) promote Aβ aggregation and tau hyperphosphorylation. The activation of mTOR signaling occurring at the early stage of AD has a prominent impact on the Aβ production. This work focused on whether BBR regulates the production and clearance of ribosylation-induced Aβ pathology via inhibiting mTOR signaling. Objective:To explore whether BBR ameliorates ribosylation-induced Aβ 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 Aβ generation and clearance. Tissue sections and Immunofluorescence staining were used to observe Aβ42 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 γ-secretase induced by D-ribose, and enhances Aβ-degrading enzymes and Neprilysin, and inhibits the expression of Aβ in APP/PS1 mice. Conclusion:BBR ameliorates ribosylation-induced Aβ pathology via inhibiting mTOR/p70S6K signaling and improves spatial learning and memory of the APP/PS1 mice.
