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

Anderson, R. et al. (2020) NLRP3 inflammasome inhibition by MCC950 in aged mice improves health via enhanced autophagy and PPARα activity. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 75(8), pp. 1457-1464. (doi: 10.1093/gerona/glz239) (PMID:31603987)

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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-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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Castejon Vega, Dr Beatriz
Authors: Anderson, R., Cordero, M. D., Bullón, P., Ruiz-Cabello, J., Robertson, A. A.B., Ryffel, B., Pérez-Pulido, A. J., Muntané, J., Pérez-Alegre, M., Andújar-Pulido, E., de la Cruz, P., Cooper, M. A., Lendines-Cordero, D., Alcocer-Gómez, E., Castejón-Vega, B., and Marín-Aguilar, F.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Journals of Gerontology Series A: Biological Sciences and Medical Sciences
Publisher:Oxford University Press
ISSN:1079-5006
ISSN (Online):1758-535X
Published Online:11 October 2019

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