| http://purl.uniprot.org/citations/25417698 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25417698 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25417698 | http://www.w3.org/2000/01/rdf-schema#comment | "Sphingosine is a major storage compound in Niemann-Pick type C disease (NP-C), although the pathological role(s) of this accumulation have not been fully characterized. Here we found that sphingosine kinase (SphK) activity is reduced in NP-C patient fibroblasts and NP-C mouse Purkinje neurons (PNs) due to defective vascular endothelial growth factor (VEGF) levels. Sphingosine accumulation due to inactivation of VEGF/SphK pathway led to PNs loss via inhibition of autophagosome-lysosome fusion in NP-C mice. VEGF activates SphK by binding to VEGFR2, resulting in decreased sphingosine storage as well as improved PNs survival and clinical outcomes in NP-C cells and mice. We also show that induced pluripotent stem cell (iPSC)-derived human NP-C neurons are generated and the abnormalities caused by VEGF/SphK inactivity in these cells are corrected by replenishment of VEGF. Overall, these results reveal a pathogenic mechanism in NP-C neurons where defective SphK activity is due to impaired VEGF levels."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncomms6514"xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncomms6514"xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "He X."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "He X."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Kim H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Kim H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Lee H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Lee H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Okada Y."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Okada Y."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Park J.H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Park J.H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Park M.H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Park M.H."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Lee J.K."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Lee J.K."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Seo E.J."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Seo E.J."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Okino N."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Okino N."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Otsu M."xsd:string |
| http://purl.uniprot.org/citations/25417698 | http://purl.uniprot.org/core/author | "Otsu M."xsd:string |