Ameliorating Ribosylation-induced Aβ Pathology by Berberine via Inhibiting mTOR/p70S6K Signaling

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background: </jats:bold>Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer’s disease (AD), inhibiting β-amyloid (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.<jats:bold>Methods:</jats:bold> 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 Aβ<jats:sub>1-42</jats:sub> in APP/PS1 mice hippocampal. Morris water maze (MWM) test was used to measure the spatial learning and memory of APP/PS1 mice.<jats:bold>Results: </jats:bold>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 BACE1and γ-secretase induced by D-ribose, and enhances Aβ-degrading enzymes and Neprilysin, and inhibits the expression of Aβin APP/PS1 mice.<jats:bold>Conclusions: </jats:bold>BBR ameliorates ribosylation-induced Aβ pathology via inhibiting mTOR/p70S6K signaling, and improves spatial learning and memory of the APP/PS1 mice.</jats:p>

Berberine Promotes TREM2-Dependent Phagocytosis of Amyloid-β By Microglia

“…However, BBR intervention can alleviate cognitive decline in AD mice by inhibiting Aβ production, Tau hyperphosphorylation and autophagy clearance [28,29]. Our previous study found that BBR ameliorates ribosylation induced Aβ pathology by inhibiting mTOR/p70S6K signaling and promoting autophagy, thereby improving spatial learning and memory in APP/PS1 mice [30].…”