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, Jesus, 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, Jesus, Bullón, Pedro and Cordero, Mario D), In The journals of gerontology. Series A, Biological sciences and medical sciences, volume 75, 2020.
Bibtex Entry:
@article{MarinAguilar:2020kv,
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, Jesus and Bull{'o}n, Pedro and Cordero, Mario D},
title = {{NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPAR$alpha$ Activity.}},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
year = {2020},
volume = {75},
number = {8},
pages = {1457--1464},
month = jul,
affiliation = {Research Laboratory, Oral Medicine Department, University of Sevilla, Seville, Spain.},
doi = {10.1093/gerona/glz239},
pmid = {31603987},
language = {English},
rating = {0},
date-added = {2020-10-13T14:50:09GMT},
date-modified = {2020-10-13T14:59:32GMT},
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.},
url = {https://academic.oup.com/biomedgerontology/article/75/8/1457/5585925},
uri = {url{papers3://publication/doi/10.1093/gerona/glz239}}
}