by Marín-Aguilar, Fabiola, Castejón-Vega, Beatriz, Alcocer-Gómez, Elísabet, Lendines-Cordero, Debora, Cooper, Matthew A., de la Cruz, Patricia, Andújar-Pulido, Eloísa, Pérez-Alegre, Mónica, Muntané, Jordi, Pérez-Pulido, Antonio J., Ryffel, Bernhard, Robertson, Avril A. B., Ruiz-Cabello, Jesús, Bullón, Pedro and Cordero, Mario D.
Abstract:
The 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-$alpha$ 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-$alpha$. 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.
Reference:
NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPAR$alpha$ Activity (Marín-Aguilar, Fabiola, Castejón-Vega, Beatriz, Alcocer-Gómez, Elísabet, Lendines-Cordero, Debora, Cooper, Matthew A., de la Cruz, Patricia, Andújar-Pulido, Eloísa, Pérez-Alegre, Mónica, Muntané, Jordi, Pérez-Pulido, Antonio J., Ryffel, Bernhard, Robertson, Avril A. B., Ruiz-Cabello, Jesús, Bullón, Pedro and Cordero, Mario D.), In The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, volume 75, 2020.
Bibtex Entry:
@article{marin-aguilar_nlrp3_2020-1,
title = {{NLRP3} {Inflammasome} {Inhibition} by {MCC950} in {Aged} {Mice} {Improves} {Health} via {Enhanced} {Autophagy} and {PPAR$alpha$} {Activity}},
volume = {75},
issn = {1758-535X},
doi = {10.1093/gerona/glz239},
abstract = {The 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-$alpha$ 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-$alpha$. 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.},
language = {eng},
number = {8},
journal = {The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences},
author = {Mar{'i}n-Aguilar, Fabiola and Castej{'o}n-Vega, Beatriz and Alcocer-G{'o}mez, El{'i}sabet and Lendines-Cordero, Debora and Cooper, Matthew A. and de la Cruz, Patricia and And{'u}jar-Pulido, Elo{'i}sa and P{'e}rez-Alegre, M{'o}nica and Muntan{'e}, Jordi and P{'e}rez-Pulido, Antonio J. and Ryffel, Bernhard and Robertson, Avril A. B. and Ruiz-Cabello, Jes{'u}s and Bull{'o}n, Pedro and Cordero, Mario D.},
month = jul,
year = {2020},
pmid = {31603987},
keywords = {Aging, Autophagy, NLRP3 inflammasome, MCC950, PPAR$alpha$},
pages = {1457--1464},
}