{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:33:54Z","timestamp":1791423234700,"version":"4.3.3"},"reference-count":60,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,5,22]],"date-time":"2014-05-22T00:00:00Z","timestamp":1400716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/deed.en_US"}],"funder":[{"DOI":"10.13039\/100012155","name":"Channel 7 Telethon Trust","doi-asserted-by":"publisher","award":["GGP 10184"],"award-info":[{"award-number":["GGP 10184"]}],"id":[{"id":"10.13039\/100012155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:p>\n                    The architecture and structural mechanics of the cell nucleus are defined by the nuclear lamina, which is formed by A\u2010 and B\u2010type lamins. Recently, gene duplication and protein overexpression of lamin B1 (LB1) have been reported in pedigrees with autosomal dominant leukodystrophy (ADLD). However, how the overexpression of LB1 affects nuclear mechanics and function and how it may result in pathology remain unexplored. Here, we report that in primary human skin fibroblasts derived from ADLD patients, LB1, but not other lamins, is overexpressed at the nuclear lamina and specifically enhances nuclear stiffness. Transient transfection of LB1 in HEK293 and neuronal N2a cells mimics the mechanical phenotype of ADLD nuclei. Notably, in ADLD fibroblasts, reducing LB1 protein levels by shRNA knockdown restores elasticity values to those indistinguishable from control fibroblasts. Moreover, isolated nuclei from ADLD fibroblasts display a reduced nuclear ion channel open probability on voltage\u2010step application, suggesting that biophysical changes induced by LB1 overexpression may alter nuclear signaling cascades in somatic cells. Overall, the overexpression of LB1 in ADLD cells alters nuclear mechanics and is linked to changes in nuclear signaling, which could help explain the pathogenesis of this disease.\u2014Ferrera, D., Canale, C., Marotta, R., Mazzaro, N., Gritti, M., Mazzanti, M., Capellari, S., Cortelli, P., Gasparini, L. Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 3906\u20103918 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-247635","type":"journal-article","created":{"date-parts":[[2014,5,24]],"date-time":"2014-05-24T00:21:03Z","timestamp":1400890863000},"page":"3906-3918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["Lamin B1 overexpression increases nuclear rigidity in autosomal dominant leukodystrophy fibroblasts"],"prefix":"10.1096","volume":"28","author":[{"given":"Denise","family":"Ferrera","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Brain Technologies Istituto Italiano di Tecnologia Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Canale","sequence":"additional","affiliation":[{"name":"Department of Nanophysics Istituto Italiano di Tecnologia Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Marotta","sequence":"additional","affiliation":[{"name":"Department of Nanochemistry Istituto Italiano di Tecnologia Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Mazzaro","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Brain Technologies Istituto Italiano di Tecnologia Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gritti","sequence":"additional","affiliation":[{"name":"Department of Biosciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Mazzanti","sequence":"additional","affiliation":[{"name":"Department of Biosciences University of Milano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Capellari","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna Clinica Neurologica, Ospedale Bellaria Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Cortelli","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna Clinica Neurologica, Ospedale Bellaria Bologna Italy"},{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Brain Technologies Istituto Italiano di Tecnologia Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.105.062554"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01357"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02728"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2012.06.001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02536.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.147330"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1872"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.5.671"},{"key":"e_1_2_7_10_1","first-page":"904","article-title":"MR characteristics and neuropathology in adult\u2010onset autosomal dominant leukodystrophy with autonomic symptoms","volume":"27","author":"Melberg A.","year":"2006","journal-title":"AJNR Am. 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