{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li Y"],"funding":["NICHD NIH HHS","NIDDK NIH HHS","NHLBI NIH HHS","Biomarin","NINDS NIH HHS","NCI NIH HHS","NIH"],"pagination":["20097-20103"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6778236"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["116(40)"],"pubmed_abstract":["Infantile globoid cell leukodystrophy (GLD, Krabbe disease) is a fatal demyelinating disorder caused by a deficiency in the lysosomal enzyme galactosylceramidase (GALC). GALC deficiency leads to the accumulation of the cytotoxic glycolipid, galactosylsphingosine (psychosine). Complementary evidence suggested that psychosine is synthesized via an anabolic pathway. Here, we show instead that psychosine is generated catabolically through the deacylation of galactosylceramide by acid ceramidase (ACDase). This reaction uncouples GALC deficiency from psychosine accumulation, allowing us to test the long-standing \"psychosine hypothesis.\" We demonstrate that genetic loss of ACDase activity (Farber disease) in the GALC-deficient mouse model of human GLD (twitcher) eliminates psychosine accumulation"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Genetic ablation of acid ceramidase in Krabbe disease confirms the psychosine hypothesis and identifies a new therapeutic target."],"pmcid":["PMC6778236"],"funding_grant_id":["N/A","T32 CA009547","NS100779","R01 NS100779","U54 HD087011","P30 DK020579","T32 HL007088","P30 HD002528","P30 DK056341"],"pubmed_authors":["Guzman MA","Crawford BE","Benitez BA","Giaramita A","Vogler CA","Elsbernd J","Fowler SC","Wozniak DF","Medin JA","Woloszynek JC","Li Y","Yip BK","Lo M","Jiang X","Babcock MC","Nagree MS","Dearborn JT","Sands MS","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"Genetic ablation of acid ceramidase in Krabbe disease confirms the psychosine hypothesis and identifies a new therapeutic target.","description":"Infantile globoid cell leukodystrophy (GLD, Krabbe disease) is a fatal demyelinating disorder caused by a deficiency in the lysosomal enzyme galactosylceramidase (GALC). GALC deficiency leads to the accumulation of the cytotoxic glycolipid, galactosylsphingosine (psychosine). Complementary evidence suggested that psychosine is synthesized via an anabolic pathway. Here, we show instead that psychosine is generated catabolically through the deacylation of galactosylceramide by acid ceramidase (ACDase). This reaction uncouples GALC deficiency from psychosine accumulation, allowing us to test the long-standing \"psychosine hypothesis.\" We demonstrate that genetic loss of ACDase activity (Farber disease) in the GALC-deficient mouse model of human GLD (twitcher) eliminates psychosine accumulation","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Oct","modification":"2026-05-01T22:42:38.951Z","creation":"2020-11-08T09:14:26Z"},"accession":"S-EPMC6778236","cross_references":{"pubmed":["31527255"],"doi":["10.1073/pnas.1912108116"]}}