Abstract
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-β (Aβ) 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-κB) p65, p-p65, TNF-α, IL-1β and Bax protein expression in Aβ25-35- or lipopolysaccharides (LPS)-treated mice and cultured Neuro-2a (N2a) cells. Moreover, RAPA disrupted Aβ25-35-induced nuclear translocation of mTOR and NF-κB. Our findings indicate that RAPA inhibits Aβ25-35- or LPS-induced neuronal inflammation through suppressing mTOR signaling and reducing nuclear import of NF-κB.
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