Alcocer-Gómez, Elísabet and Castejón-Vega, Beatriz and Nuñez-Vasco, Jéssica and Lendines-Cordero, Débora and Navarro-Pando, José M. and Cordero, Mario D. UNSPECIFIED, UNSPECIFIED, UNSPECIFIED, UNSPECIFIED, jose.navarro@uneatlantico.es, mario.cordero@uneatlantico.es (2020) NLRP3 inflammasome inhibition rescues Hutchinson-Gilford Progeria cellular phenotype and extend longevity of an animal model. bioRxiv (preprints). (Unpublished)
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Abstract
Inflammation is a hallmark of aging and accelerated aging syndromes. In this context, inflammation has been associated to the pathophysiology of Hutchinson–Gilford progeria syndrome (HGPS). In this study, we report that progeroid skin fibroblasts and animal models present an hyperactivation of the NLRP3-inflammasome complex. High expression of NLRP3 and caspase 1 was also observed in skin fibroblasts from HGPS associated to the nuclei morphology. Lymphoblast from HGPS also showed increased basal levels of NLRP3 and caspase 1 independent to the induction from metabolic factors. Consistent with these results, Zmpste24−/− showed high expression of Nlrp3 and caspase 1 in heart, liver and kidney and reduced levels of Nlrc3, however these changes were not observed in other inflammasomes. We also show that pharmacological inhibition of NLRP3 using a direct NLRP3 inhibitor, MCC950, improved cellular phenotype, significantly extends the lifespan of these progeroid animals and reduced inflammasome-dependent inflammation. These findings suggest the NLRP3-inflammasome comples as a therapeutic approach for patients with HGPS.
| Item Type: | Article |
|---|---|
| Commentary on: | Eprints 0 not found. |
| Additional Information: | Inmunology |
| Subjects: | Subjects > Biomedicine |
| Divisions: | Europe University of Atlantic > Research > Scientific Production |
| SWORD Depositor: | Users 0 not found. |
| Depositing User: | Sr Bibliotecario |
| Date Deposited: | 20 May 2021 11:08 |
| Last Modified: | 30 Jun 2023 14:49 |
| URI: | http://repositorio.funiber.org/id/eprint/111 |
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- NLRP3 inflammasome inhibition rescues Hutchinson-Gilford Progeria cellular phenotype and extend longevity of an animal model. (deposited 20 May 2021 11:08) [Currently Displayed]
Commentary/Response Threads
- Alcocer-Gómez, Elísabet and Castejón-Vega, Beatriz and Nuñez-Vasco, Jéssica and Lendines-Cordero, Débora and Navarro-Pando, José M. and Cordero, Mario D. NLRP3 inflammasome inhibition rescues Hutchinson-Gilford Progeria cellular phenotype and extend longevity of an animal model. (deposited 20 May 2021 11:08) [Currently Displayed]
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