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 |
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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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