| |  Online-Ressource |
|---|
| Verfasst von: | Lee, Hyun [VerfasserIn]  |
|---|
| | Lee, Jong Kil [VerfasserIn] |
|---|
| | Park, Min Hee [VerfasserIn] |
|---|
| | Hong, Yu Ri [VerfasserIn] |
|---|
| | Marti, Hugo [VerfasserIn] |
|---|
| | Kim, Hyongbum [VerfasserIn] |
|---|
| | Okada, Yohei [VerfasserIn] |
|---|
| | Otsu, Makoto [VerfasserIn] |
|---|
| | Seo, Eul-Ju [VerfasserIn] |
|---|
| | Park, Jae-Hyung [VerfasserIn] |
|---|
| | Bae, Jae-Hoon [VerfasserIn] |
|---|
| | Okino, Nozomu [VerfasserIn] |
|---|
| | He, Xingxuan [VerfasserIn] |
|---|
| | Schuchman, Edward H. [VerfasserIn] |
|---|
| | Bae, Jae-sung [VerfasserIn] |
|---|
| | Jin, Hee Kyung [VerfasserIn] |
|---|
| Titel: | Pathological roles of the VEGF/SphK pathway in Niemann-Pick type C neurons |
|---|
| Verf.angabe: | Hyun Lee, Jong Kil Lee, Min Hee Park, Yu Ri Hong, Hugo H. Marti, Hyongbum Kim, Yohei Okada, Makoto Otsu, Eul-Ju Seo, Jae-Hyung Park, Jae-Hoon Bae, Nozomu Okino, Xingxuan He, Edward H. Schuchman, Jae-sung Bae & Hee Kyung Jin |
|---|
| E-Jahr: | 2014 |
|---|
| Jahr: | 24 November 2014 |
|---|
| Umfang: | 17 S. |
|---|
| Teil: | volume:5 |
|---|
| | year:2014 |
|---|
| | extent:17 |
|---|
| Fussnoten: | Gesehen am 11.12.2020 |
|---|
| Titel Quelle: | Enthalten in: Nature Communications |
|---|
| Ort Quelle: | [London] : Nature Publishing Group UK, 2010 |
|---|
| Jahr Quelle: | 2014 |
|---|
| Band/Heft Quelle: | 5(2014) Artikel-Nummer 5514, 17 Seiten |
|---|
| ISSN Quelle: | 2041-1723 |
|---|
| Abstract: | 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. |
|---|
| DOI: | doi:10.1038/ncomms6514 |
|---|
| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1038/ncomms6514 |
|---|
| | Volltext: https://www.nature.com/articles/ncomms6514 |
|---|
| | DOI: https://doi.org/10.1038/ncomms6514 |
|---|
| Datenträger: | Online-Ressource |
|---|
| Sprache: | eng |
|---|
| K10plus-PPN: | 1742617336 |
|---|
| Verknüpfungen: | → Zeitschrift |
|---|
Pathological roles of the VEGF/SphK pathway in Niemann-Pick type C neurons / Lee, Hyun [VerfasserIn]; 24 November 2014 (Online-Ressource)
