RAPAMYCIN SUPPRESSES Aβ25-35- OR LPS-INDUCED NEURONAL INFLAMMATION VIA MODULATION OF NF-KB SIGNALING

Rapamycin (RAPA), an inhibitor of mammalian target of rapamycin (mTOR), exhibits a high neuroprotective action against neurodegenerative diseases in mouse models. Since neuroinflammation has been shown to be involved in Alzheimer's disease (AD) development and progression, the aim of this study was to examine the anti-inflammatory role of RAPA in AD in vivo and in vitro, and investigate the underlying mechanisms. We found that amyloid-beta (A beta) induced neuronal inflammation and a remarkable increase in mTOR activity in in-vivo and in-vitro models of inflammation, suggesting the critical role of mTOR signaling in neuronal inflammation. In addition, administration of RAPA was found to down-regulate mTOR, p-mTOR, Nuclear factor kappa B (NF-kappa B) p65, p-p65, TNF-alpha, IL-1 beta and Bax protein expression in AP(25-35)-or lipopolysaccharides (LPS)treated mice and cultured Neuro-2a (N2a) cells. Moreover, RAPA disrupted A(25-35)-induced nuclear translocation of mTOR and NF-kappa B. Our findings indicate that RAPA inhibits A beta(25-35)- or LPS-induced neuronal inflammation through suppressing mTOR signaling and reducing nuclear import of NF-KB. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.