{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:14:40Z","timestamp":1783059280830,"version":"3.54.6"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>CLN3 disease is the commonest of the neuronal ceroid lipofuscinoses, a group of pediatric neurodegenerative disorders. Functions of the CLN3 protein include antiapoptotic properties and facilitating anterograde transport of galactosylceramide from Golgi to lipid rafts. This study confirms the beneficial effects of long\u2010term exogenous galactosylceramide supplementation on longevity, neurobehavioral parameters, neuronal cell counts, astrogliosis, and diminution in brain and serum ceramide levels in <jats:italic>Cln3<\/jats:italic><jats:sup>\n<jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> knock\u2010in mice. Additionally, the impact of galactosylceramide on ceramide synthesis enzymes is documented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A group of 72 mice received galactosylceramide or vehicle for 40\u2009weeks. The effect of galactosylceramide supplementation on <jats:italic>Cln3<\/jats:italic><jats:sup>\n<jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> mice was determined by performing behavioral tests, measuring ceramide in brains and serum, and assessing impact on longevity, subunit C storage, astrogliosis, and neuronal cell counts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Galactosylceramide resulted in enhanced grip strength of forelimbs in male and female mice, better balance on the accelerating rotarod in females, and improved motor coordination during pole climbing in male mice. Brain and serum ceramide levels as well as apoptosis rates were lower in galactosylceramide\u2010treated <jats:italic>Cln3<\/jats:italic><jats:sup>\n<jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> mice. Galactosylceramide also increased neuronal cell counts significantly in male and female mice and tended to decrease subunit C storage in specific brain regions. Astrogliosis dropped in females compared to a slight increase in males after galactosylceramide. Galactosylceramide increased the lifespan of affected mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Galactosylceramide improved behavioral, neuropathological, and biochemical parameters in <jats:italic>Cln3<\/jats:italic><jats:sup>\n<jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> mice, paving the way for effective therapy for CLN3 disease and use of serum ceramide as a potential biomarker to track impact of therapies. ANN NEUROL 2019;86:729\u2013742<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25573","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T15:23:32Z","timestamp":1565277812000},"page":"729-742","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exogenous Galactosylceramide as Potential Treatment for CLN3 Disease"],"prefix":"10.1002","volume":"86","author":[{"given":"Sally","family":"El\u2010Sitt","sequence":"first","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihane","family":"Soueid","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Maalouf","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Makhoul","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Al Ali","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Makoukji","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Asser","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Daou","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayat","family":"Harati","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Medical School, Lebanese University  Hadath Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2066-0079","authenticated-orcid":false,"given":"Rose\u2010Mary","family":"Boustany","sequence":"additional","affiliation":[{"name":"Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine American University of Beirut Medical Center  Beirut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.1.1"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/514846"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570243"},{"key":"e_1_2_8_5_1","first-page":"654","article-title":"Batten disease gene, CLN3: linkage disequilibrium mapping in the Finnish population, and analysis of European haplotypes","volume":"56","author":"Mitchison HM","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-005-0218-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67020677.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.01.011"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-005-0733-6"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.18.2129"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000136152.54638.95"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e31816fdc17"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-6741-1_1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973664"},{"key":"e_1_2_8_15_1","unstructured":"HaratiH CotmanS BoustanyRM. Galactosylceramide (GalCer ) as a potential treatment for juvenile neuronal ceroid lipofuscinosis (JNCL). Abstract presented at: 13'th International Conference on Neuronal Ceroid Lipofuscinosis (Batten Disease) 28th\u201031st March 2012 Royal Holloway College London UK."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng015"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1027"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.32607\/20758251-2015-7-2-42-47"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038310"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.22.2709"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.05.018"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2009.00478.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2013.765421"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9421-6"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01273267"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1999.0267"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.07.030"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021643"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.05.010"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9297-x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.03.014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00128"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.08.017"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2001.1099"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.11.008"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.25573","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T12:52:34Z","timestamp":1694177554000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.25573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,28]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,11]]}},"alternative-id":["10.1002\/ana.25573"],"URL":"https:\/\/doi.org\/10.1002\/ana.25573","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,28]]},"assertion":[{"value":"2019-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}