{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:23:16Z","timestamp":1790043796917,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T00:00:00Z","timestamp":1400544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Italian Ministry of Health","award":["RF-2010-2314356"],"award-info":[{"award-number":["RF-2010-2314356"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified a homozygous nonsynonymous mutation in <jats:italic>CERS1<\/jats:italic>, the gene encoding ceramide synthase 1, in 4 siblings affected by a progressive disorder with myoclonic epilepsy and dementia. CerS1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18\u2010ceramides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that the mutation decreases C18\u2010ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This study demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. Ann Neurol 2014;76:206\u2013212<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24170","type":"journal-article","created":{"date-parts":[[2014,4,30]],"date-time":"2014-04-30T09:06:52Z","timestamp":1398848812000},"page":"206-212","source":"Crossref","is-referenced-by-count":95,"title":["Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy"],"prefix":"10.1002","volume":"76","author":[{"given":"Nicola","family":"Vanni","sequence":"first","affiliation":[{"name":"Department of Neuroscience Institute G. Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriana","family":"Fruscione","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Institute G. 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