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FTY720\/ fingolimod, used for treatment of multiple sclerosis, is phosphorylated by nuclear sphingosine kinase 2, and its active phosphorylated form (FTY720\u2010P) is an inhibitor of class I histone deacetylases. In this study, administration of clinically relevant doses of FTY720 to mice increased expression of NPC1 and \u22122 in brain and liver and decreased cholesterol in an SphK2\u2010dependent manner. FTY720 greatly increased expression of NPC1 and \u22122 in human\n                    <jats:italic>NPC1<\/jats:italic>\n                    mutant fibroblasts that correlated with formation of FTY720\u2010P and significantly reduced the accumulation of cholesterol and glycosphingolipids. In agreement with this finding, FTY720 pretreatment of human\n                    <jats:italic>NPC1<\/jats:italic>\n                    mutant fibroblasts restored transport of the cholera toxin B subunit, which binds ganglioside GM1, to the Golgi apparatus. Together, these findings suggest that FTY720 administration can ameliorate cholesterol and sphingolipid storage and trafficking defects in\n                    <jats:italic>NPC1<\/jats:italic>\n                    mutant fibroblasts. Because neurodegeneration is the main clinical feature of NPC disease, and FTY720 accumulates in the CNS and has several advantages over available histone deacetylase inhibitors now in clinical trials, our work provides a potential opportunity for treatment of this incurable disease. \u2014Newton, J., Hait, N. C., Maceyka, M., Colaco, A., Maczis, M., Wassif, C. A., Cougnoux, A., Porter, F. D., Milstien, S., Platt, N., Platt, F. M., Spiegel, S. FTY720\/fingolimod increases NPC1 and NPC2 expression and reduces cholesterol and sphingolipid accumulation in Niemann\u2010Pick type C mutant fibroblasts.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 31, 1719\u20131730 (2017)\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.201601041r","type":"journal-article","created":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T22:10:34Z","timestamp":1484259034000},"page":"1719-1730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["FTY720\/fingolimod increases NPC1 and NPC2 expression and reduces cholesterol and sphingolipid accumulation in Niemann\u2010Pick type C mutant fibroblasts"],"prefix":"10.1096","volume":"31","author":[{"given":"Jason","family":"Newton","sequence":"first","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitai C.","family":"Hait","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"},{"name":"Department of Oncology Roswell Park Cancer Institute  Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Maceyka","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria","family":"Colaco","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Maczis","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Wassif","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Cougnoux","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon","family":"Milstien","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford  Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Spiegel","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry and Molecular Biology Virginia Commonwealth University School of Medicine  Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.05.016"},{"key":"e_1_2_8_3_1","article-title":"Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice","volume":"108","author":"Xie X.","year":"2011","journal-title":"Proc. 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