{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:11:44Z","timestamp":1791288704762,"version":"4.3.0"},"reference-count":84,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["577668"],"award-info":[{"award-number":["577668"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Thierry Latran","award":["00099187"],"award-info":[{"award-number":["00099187"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disorder of the motor system. While the etiology is still incompletely understood, defects in metabolism act as a major contributor to the disease progression. Recently, histone deacetylase (HDAC) inhibition using ACY-738 has been shown to restore metabolic alterations in the spinal cord of a FUS mouse model of ALS, which was accompanied by a beneficial effect on the motor phenotype and survival. In this study, we investigated the specific effects of HDAC inhibition on lipid metabolism using untargeted lipidomic analysis combined with transcriptomic analysis in the spinal cord of FUS mice. We discovered that symptomatic FUS mice recapitulate lipid alterations found in ALS patients and in the SOD1 mouse model. Glycerophospholipids, sphingolipids, and cholesterol esters were most affected. Strikingly, HDAC inhibition mitigated lipid homeostasis defects by selectively targeting glycerophospholipid metabolism and reducing cholesteryl esters accumulation. Therefore, our data suggest that HDAC inhibition is a potential new therapeutic strategy to modulate lipid metabolism defects in ALS and potentially other neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms222011224","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T22:52:47Z","timestamp":1634683967000},"page":"11224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Histone Deacetylase Inhibition Regulates Lipid Homeostasis in a Mouse Model of Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8788-2936","authenticated-orcid":false,"given":"Thibaut","family":"Burg","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"Center for Brain & Disease Research, Laboratory of Neurobiology, VIB, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Rossaert","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"Center for Brain & Disease Research, Laboratory of Neurobiology, VIB, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Moisse","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"Center for Brain & Disease Research, Laboratory of Neurobiology, VIB, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-2357","authenticated-orcid":false,"given":"Philip","family":"Van Damme","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"Center for Brain & Disease Research, Laboratory of Neurobiology, VIB, 3000 Leuven, Belgium"},{"name":"Department of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-4067","authenticated-orcid":false,"given":"Ludo","family":"Van Den Bosch","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"Center for Brain & Disease Research, Laboratory of Neurobiology, VIB, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: A clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur. 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