{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:24:52Z","timestamp":1789647892344,"version":"4.0.0"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002287","name":"Progeria Research Foundation","doi-asserted-by":"publisher","award":["PRF 2021\u201078"],"award-info":[{"award-number":["PRF 2021\u201078"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of the inflammasomes in aging and progeroid syndromes remain understudied. Recently, MCC950, a NLRP3 inhibitor, was used in Zmpste24<jats:sup>\u2212\/\u2212<\/jats:sup> mice to ameliorate the phenotypes. However, the safety of MCC950 was questioned due to liver toxicity observed in humans. Nevertheless, inhibition of the inflammasomes would be a beneficial therapy for progeria. Here, we show that OLT1177 (dapansutrile), other NLRP3 inhibitor, improved cellular and animal phenotypes using progeroid fibroblasts and a Lmna<jats:sup>G609G\/G609G<\/jats:sup> mouse model. In both cases dapansutrile reduced progerin accumulation, NLRP3\u2010inflammasome activation and secretory phenotype of senescence, extended the lifespan of progeroid animals, preserved bodyweight, and reduced kyphosis, inflammation, and senescence. Interestingly, dapansutrile further improved the effect of lonafarnib, the only FDA\u2010approved drug for the progeria. The combination of both drugs reduced the inflammation and senescence, extended survival and ameliorated various progeroid defects both in\u00a0vitro and in\u00a0vivo, compared with treatment using lonafarnib alone. These findings and the safety of dapansutrile demonstrated in several clinical trials proposes it as a possible co\u2010adjuvant treatment with lonafarnid in HGPS.<\/jats:p>","DOI":"10.1111\/acel.14272","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T05:40:31Z","timestamp":1724823631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The <scp>NLRP3<\/scp> inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice"],"prefix":"10.1111","volume":"23","author":[{"given":"In\u00e9s","family":"Muela\u2010Zarzuela","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Miguel","family":"Suarez\u2010Rivero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Boy\u2010Ruiz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"L\u00f3pez\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Immunology Puerta del Mar Hospital  C\u00e1diz Spain"},{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz, INiBICA Hospital Universitario Puerta del Mar  C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sotelo\u2010Montoro","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"del Mar\u00a0Navarrete\u2010Alonso","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidro G.","family":"Collado","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Ciencias, Campus Universitario R\u00edo San Pedro s\/n, Torre Sur, 4a Planta University of C\u00e1diz  C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Botubol\u2010Ares","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica, Facultad de Ciencias, Campus Universitario R\u00edo San Pedro s\/n, Torre Sur, 4a Planta University of C\u00e1diz  C\u00e1diz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Sanz","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0151-3644","authenticated-orcid":false,"given":"Mario D.","family":"Cordero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26123534"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147474"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051201"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13903"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.990469"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506001102"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.10.009"},{"key":"e_1_2_10_9_1","first-page":"26","article-title":"Could an NLRP3 inhibitor Be the one drug to conquer common diseases?","volume":"98","author":"Coss R.","year":"2020","journal-title":"C EN Glob. Enterp"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402943101"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114012"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12101350"},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","unstructured":"Jansen T. L. Kl\u00fcck V. Janssen M. Comarniceanu A. Efd\u00e9 M. Scribner C. L. Barrow R. B. Skouras D. B. Dinarello C. A. &Joosten L. A.(2019).P160 the first phase 2A proof\u2010of\u2010concept study of a selective NLRP3 inflammasome inhibitor dapansutrile\u2122(OLT1177\u2122) Acute Gout. 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