{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:24:53Z","timestamp":1791894293285,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T00:00:00Z","timestamp":1418688000000},"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":"crossref","award":["2012-44"],"award-info":[{"award-number":["2012-44"]}],"id":[{"id":"10.13039\/100002287","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2015,2]]},"abstract":"Summary<\/jats:title>\n \n Hutchinson\u2013Gilford progeria syndrome (\n HGPS<\/jats:styled-content>\n ,\n OMIM<\/jats:styled-content>\n 176670) is a rare multisystem childhood premature aging disorder linked to mutations in the\n \n LMNA<\/jats:styled-content>\n <\/jats:italic>\n gene. The most common\n HGPS<\/jats:styled-content>\n mutation is found at position G608G within exon 11 of the\n \n LMNA<\/jats:styled-content>\n <\/jats:italic>\n gene. This mutation results in the deletion of 50 amino acids at the carboxyl\u2010terminal tail of prelamin A, and the truncated protein is called\n progerin<\/jats:italic>\n . Progerin only undergoes a subset of the normal post\u2010translational modifications and remains permanently farnesylated. Several attempts to rescue the normal cellular phenotype with farnesyltransferase inhibitors (\n FTI<\/jats:styled-content>\n s) and other compounds have resulted in partial cellular recovery. Using proteomics, we report here that progerin induces changes in the composition of the\n HGPS<\/jats:styled-content>\n nuclear proteome, including alterations to several components of the protein degradation pathways. Consequently, proteasome activity and autophagy are impaired in\n HGPS<\/jats:styled-content>\n cells. To restore protein clearance in\n HGPS<\/jats:styled-content>\n cells, we treated\n HGPS<\/jats:styled-content>\n cultures with sulforaphane (SFN), an antioxidant derived from cruciferous vegetables. We determined that SFN stimulates proteasome activity and autophagy in normal and\n HGPS<\/jats:styled-content>\n fibroblast cultures. Specifically, SFN enhances progerin clearance by autophagy and reverses the phenotypic changes that are the hallmarks of\n HGPS<\/jats:styled-content>\n . Therefore, SFN is a promising therapeutic avenue for children with\n HGPS<\/jats:styled-content>\n .\n <\/jats:p>","DOI":"10.1111\/acel.12300","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T05:01:49Z","timestamp":1418706109000},"page":"78-91","source":"Crossref","is-referenced-by-count":113,"title":["Sulforaphane enhances progerin clearance in\n H<\/scp>\n utchinson\u2013\n G<\/scp>\n ilford progeria fibroblasts"],"prefix":"10.1111","volume":"14","author":[{"given":"Diana","family":"Gabriel","sequence":"first","affiliation":[{"name":"Department of Medicine Epigenetics of skin Aging and Institute for Medical Engineering Technische Universit\u00e4t M\u00fcnchen (TUM) Garching bei M\u00fcnchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Roedl","sequence":"additional","affiliation":[{"name":"Department of Medicine Epigenetics of skin Aging and Institute for Medical Engineering Technische Universit\u00e4t M\u00fcnchen (TUM) Garching bei M\u00fcnchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie B.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Alpert Medical School of Brown University and Hasbro Children's Hospital Providence RI USA"},{"name":"Boston Children's Hospital and Harvard University Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Djabali","sequence":"additional","affiliation":[{"name":"Department of Medicine Epigenetics of skin Aging and Institute for Medical Engineering Technische Universit\u00e4t M\u00fcnchen (TUM) Garching bei M\u00fcnchen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-011-0674-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2013-0168"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2008.029"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43578"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002346"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506001102"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807840105"},{"key":"e_1_2_9_9_1","first-page":"200","article-title":"Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin\u2010linked progeria","volume":"55","author":"Cenni V","year":"2011","journal-title":"Eur. 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