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Title

NLRP3 inflammasome inhibition by MCC950 in aged mice improves health via enhanced autophagy and PPARα activity

AuthorsMarín-Aguilar, Fabiola; Castejón-Vega, Beatriz; Alcocer-Gómez, Elísabet; Lendines-Cordero, Debora; Cooper, Matthew A.; Cruz, Patricia de la; Andújar-Pulido, Eloísa; Pérez-Alegre, Mónica ; Muntané, Jordi; Pérez-Pulido, Antonio J. ; Ryffel, Bernhard; Robertson, Avril A. B.; Ruiz-Cabello, Jesús; Bullón, Pedro; Cordero, Mario D.
Issue Date2019
PublisherOxford University Press
CitationJournal of Gerontology 75(8): 1457–1464 (2019)
AbstractThe NLRP3 inflammasome has emerged as an important regulator of metabolic disorders and age-related diseases in NLRP3-deficient mice. In this article, we determine whether, in old mice C57BL6J, the NLRP3 inflammasome inhibitor MCC950 is able to attenuate age-related metabolic syndrome to providing health benefits. We report that MCC950 attenuates metabolic and hepatic dysfunction in aged mice. In addition, MCC950 inhibited the Pi3K/AKT/mTOR pathway, enhanced autophagy, and activated peroxisome proliferator-activated receptor-α in vivo and in vitro. The data suggest that MCC950 mediates the protective effects by the mammalian target of rapamycin inhibition, thus activating autophagy and peroxisome proliferator-activated receptor-α. In conclusion, pharmacological inhibition of NLRP3 in aged mice has a significant impact on health. Thus, NLRP3 may be a therapeutic target of human age-related metabolic syndrome.
Publisher version (URL)https://doi.org/10.1093/gerona/glz239
URIhttp://hdl.handle.net/10261/221212
DOI10.1093/gerona/glz239
ISSN0022-1422
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