Ameliorating Ribosylation-Induced Amyloid-Beta Pathology By Berberine Via Inhibiting Mtor/P70s6k Signaling

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.