{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:00:14Z","timestamp":1785247214123,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007393","name":"French Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["AFM grant MNH\u2010Decrypt 2011\u20102015 and TRIM\u2010RD 2016\u20102020 to A.D.S.G. and N.L."],"award-info":[{"award-number":["AFM grant MNH\u2010Decrypt 2011\u20102015 and TRIM\u2010RD 2016\u20102020 to A.D.S.G. and N.L."]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"publisher","award":["recurrent grants"],"award-info":[{"award-number":["recurrent grants"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007587","name":"Aix-Marseille University","doi-asserted-by":"publisher","award":["recurrent grants"],"award-info":[{"award-number":["recurrent grants"]}],"id":[{"id":"10.13039\/100007587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Progeroid syndromes (PS), including Hutchinson-Gilford Progeria Syndrome (HGPS), are premature and accelerated aging diseases, characterized by clinical features mimicking physiological aging. Most classical HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type lamins. This mutation activates a cryptic splice site, leading to the production of a truncated prelamin A, called prelamin A \u220650 or progerin, that accumulates in HGPS cell nuclei and is a hallmark of the disease. Some patients with PS carry other LMNA mutations and are named \u201cHGPS-like\u201d patients. They produce progerin and\/or other truncated prelamin A isoforms (\u220635 and \u220690). We previously found that MG132, a proteasome inhibitor, induced progerin clearance in classical HGPS through autophagy activation and splicing regulation. Here, we show that MG132 induces aberrant prelamin A clearance and improves cellular phenotypes in HGPS-like patients\u2019 cells other than those previously described in classical HGPS. These results provide preclinical proof of principle for the use of a promising class of molecules toward a potential therapy for children with HGPS-like or classical HGPS.<\/jats:p>","DOI":"10.3390\/cells11040610","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T02:37:46Z","timestamp":1644547066000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MG132 Induces Progerin Clearance and Improves Disease Phenotypes in HGPS-like Patients\u2019 Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2904-5221","authenticated-orcid":false,"given":"Karim","family":"Harhouri","sequence":"first","affiliation":[{"name":"Marseille Medical Genetics (MMG), INSERM U 1251, Aix Marseille Universit\u00e9, 13005 Marseille, France"},{"name":"Progelife, 13002 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4334-2014","authenticated-orcid":false,"given":"Pierre","family":"Cau","sequence":"additional","affiliation":[{"name":"Progelife, 13002 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Casey","sequence":"additional","affiliation":[{"name":"Royal Belfast, Pediatric Cardiology, Hospital for Sick Children, Belfast BT9 7AB, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-7610","authenticated-orcid":false,"given":"Koffi Mawuse","family":"Guedenon","sequence":"additional","affiliation":[{"name":"CHU Sylvanus Olympio de Lom\u00e9, Unit\u00e9 de G\u00e9n\u00e9tique Humaine, Lom\u00e9 BP 1515, Togo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassamine","family":"Doubaj","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale, Institut National d\u2019Hygi\u00e8ne, Rabat 11400, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Van Maldergem","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique Humaine, CHU Universit\u00e9 de Franche-Comt\u00e9, 25000 Besancon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Mejia-Baltodano","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Ministerio de Salud de Nicaragua, Hospital Infantil \u201cManuel de Jes\u00fas Rivera\u201d, Managua 12079, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Bartoli","sequence":"additional","affiliation":[{"name":"Marseille Medical Genetics (MMG), INSERM U 1251, Aix Marseille Universit\u00e9, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-2462","authenticated-orcid":false,"given":"Annachiara","family":"De Sandre-Giovannoli","sequence":"additional","affiliation":[{"name":"Marseille Medical Genetics (MMG), INSERM U 1251, Aix Marseille Universit\u00e9, 13005 Marseille, France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital d\u2019Enfants de la Timone, AP-HM, 13005 Marseille, France"},{"name":"Biological Resource Center (CRB-TAC), Assistance Publique H\u00f4pitaux de Marseille, La Timone Children\u2019s Hospital, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"L\u00e9vy","sequence":"additional","affiliation":[{"name":"Marseille Medical Genetics (MMG), INSERM U 1251, Aix Marseille Universit\u00e9, 13005 Marseille, France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital d\u2019Enfants de la Timone, AP-HM, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1002\/ajmg.a.31346","article-title":"Hutchinson-Gilford progeria syndrome: Review of the phenotype","volume":"140","author":"Hennekam","year":"2006","journal-title":"Am. 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