RT Journal Article
T1 Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson-Gilford Progeria
A1 González-Domínguez, Álvaro
A1 Montañez, Raúl
A1 Castejón-Vega, Beatriz
A1 Nuñez-Vasco, Jéssica
A1 Lendines-Cordero, Débora
A1 Chun, Wang
A1 Mbalaviele, Gabriel
A1 Navarro-Pando, José M.
A1 Alcocer-Gomez, Elísabet
A1 Cordero, Mario
K1 Inflamación (Patología)
K1 Envejecimiento
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 2021-10-07
LK https://hdl.handle.net/10630/35316
UL https://hdl.handle.net/10630/35316
LA eng
NO Alvaro González‐Dominguez, Raúl Montañez, Beatriz Castejón‐Vega, Jéssica Nuñez‐Vasco, Débora Lendines‐Cordero, Chun Wang, Gabriel Mbalaviele, José M Navarro‐Pando, Elísabet Alcocer‐Gómez, and Mario D Cordero. Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson–Gilford Progeria. EMBO Mol Med (2021) 13: e14012 https://doi.org/10.15252/emmm.202114012
NO This study was supported by a grant from the Progeria Research Foundation PRF 2021‐ 80 grant, Andalusian regional government (Grupo de Investigacion Junta de Andalucia CTS113 and Consejería de Salud de la Junta de Andalucia: PI‐0036‐2014). Dr. Gabriel Mbalaviele was supported by NIH/NIAMS AR068972 and AR076758 grants.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026