Rapamycin suppresses Aβ 25-35 - or LPS-induced neuronal inflammation via modulation of NF-κB signaling.

Autor: Liu YC; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Town, Minhou County, Fuzhou City, Fujian Province 350108, China., Gao XX; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Town, Minhou County, Fuzhou City, Fujian Province 350108, China., Chen L; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Town, Minhou County, Fuzhou City, Fujian Province 350108, China., You XQ; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Fujian Medical University, No. 1 Xueyuan Road, Shangjie Town, Minhou County, Fuzhou City, Fujian Province 350108, China. Electronic address: yxqtr@163.com.
Jazyk: angličtina
Zdroj: Neuroscience [Neuroscience] 2017 Jul 04; Vol. 355, pp. 188-199. Date of Electronic Publication: 2017 May 11.
DOI: 10.1016/j.neuroscience.2017.05.005
Abstrakt: 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 Aβ 25-35 - or lipopolysaccharides (LPS)-treated mice and cultured Neuro-2a (N2a) cells. Moreover, RAPA disrupted Aβ 25-35 -induced nuclear translocation of mTOR and NF-κB. Our findings indicate that RAPA inhibits Aβ 25-35 - or LPS-induced neuronal inflammation through suppressing mTOR signaling and reducing nuclear import of NF-κB.
(Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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