RT Journal Article
T1 Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson-Gilford Progeria
A1 González-Dominguez, Alvaro
A1 Montañez, Raúl
A1 Castejón-Vega, Beatriz
A1 Nuñez-Vasco, Jéssica
A1 Lendines-Cordero, Débora
A1 Wang, Chun
A1 Mbalaviele, Gabriel
A1 Navarro-Pando, José M.
A1 Alcocer-Gómez, Elísabet
A1 Cordero, Mario D.
K1 Aging
K1 NLRP3
K1 Inflammasome
K1 Progeria
K1 Caspase 1
K1 Longevity
K1 Fibroblasts
K1 Phenotype
K1 Lamin A
K1 Envejecimiento
K1 Proteína con dominio pirina 3 de la familia NLR
K1 Inflamasomas
K1 Caspase 1
K1 Longevidad
K1 Fibroblastos
K1 Fenotipo
K1 Lamina tipo A
AB Inflammation is a hallmark of aging and accelerated aging syndromes such as Hutchinson-Gilford progeria syndrome (HGPS). In this study, we present evidence of increased expression of the components of the NLRP3 inflammasome pathway in HGPS skin fibroblasts, an outcome that was associated with morphological changes of the nuclei of the cells. Lymphoblasts from HGPS patients also showed increased basal levels of NLRP3 and caspase 1. Consistent with these results, the expression of caspase 1 and Nlrp3, but not of the other inflammasome receptors was higher in the heart and liver of Zmpste24-/- mice, which phenocopy the human disease. These data were further corroborated in LmnaG609G/G609G mice, another HGPS animal model. We also showed that pharmacological inhibition of the NLRP3 inflammasome by its selective inhibitor, MCC950, improved cellular phenotype, significantly extended the lifespan of progeroid animals, and reduced inflammasome-dependent inflammation. These findings suggest that inhibition of the NLRP3 inflammasome is a potential therapeutic approach for the treatment of HGPS.
PB EMBO Press
YR 2021
FD 2021-08-27
LK http://hdl.handle.net/10668/4355
UL http://hdl.handle.net/10668/4355
LA en
NO González-Dominguez A, Montañez R, Castejón-Vega B, Nuñez-Vasco J, Lendines-Cordero D, Wang C, et al. Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson-Gilford Progeria. EMBO Mol Med. 2021 Oct 7;13(10):e14012
DS RISalud
RD Apr 18, 2025