NLRP3 Inflammasome Inhibition by MCC950 in Aged Mice Improves Health via Enhanced Autophagy and PPARα Activity.
J Gerontol A Biol Sci Med Sci
; 75(8): 1457-1464, 2020 07 13.
Article
in En
| MEDLINE
| ID: mdl-31603987
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
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Sulfones
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PPAR alpha
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Inflammasomes
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NLR Family, Pyrin Domain-Containing 3 Protein
/
Heterocyclic Compounds, 4 or More Rings
Limits:
Animals
Language:
En
Journal:
J Gerontol A Biol Sci Med Sci
Journal subject:
GERIATRIA
Year:
2020
Document type:
Article
Affiliation country:
Spain