| |  Online-Ressource |
|---|
| Verfasst von: | Pepe, Giuseppe [VerfasserIn]  |
|---|
| | Capocci, Luca [VerfasserIn] |
|---|
| | Marracino, Federico [VerfasserIn] |
|---|
| | Realini, Natalia [VerfasserIn] |
|---|
| | Lenzi, Paola [VerfasserIn] |
|---|
| | Martinello, Katiuscia [VerfasserIn] |
|---|
| | Bovier, Tiziana Francesca [VerfasserIn] |
|---|
| | Bichell, Terry Jo [VerfasserIn] |
|---|
| | Scarselli, Pamela [VerfasserIn] |
|---|
| | Di Cicco, Clotilde [VerfasserIn] |
|---|
| | Bowman, Aaron B. [VerfasserIn] |
|---|
| | Digilio, Filomena A. [VerfasserIn] |
|---|
| | Fucile, Sergio [VerfasserIn] |
|---|
| | Fornai, Francesco [VerfasserIn] |
|---|
| | Armirotti, Andrea [VerfasserIn] |
|---|
| | Parlato, Rosanna [VerfasserIn] |
|---|
| | Di Pardo, Alba [VerfasserIn] |
|---|
| | Maglione, Vittorio [VerfasserIn] |
|---|
| Titel: | Treatment with THI, an inhibitor of sphingosine-1-phosphate lyase, modulates glycosphingolipid metabolism and results therapeutically effective in experimental models of Huntington’s disease |
|---|
| Verf.angabe: | Giuseppe Pepe, Luca Capocci, Federico Marracino, Natalia Realini, Paola Lenzi, Katiuscia Martinello, Tiziana Francesca Bovier, Terry Jo Bichell, Pamela Scarselli, Clotilde Di Cicco, Aaron B. Bowman, Filomena A. Digilio, Sergio Fucile, Francesco Fornai, Andrea Armirotti, Rosanna Parlato, Alba Di Pardo, Vittorio Maglione |
|---|
| E-Jahr: | 2023 |
|---|
| Jahr: | 4 January 2023 |
|---|
| Umfang: | 18 S. |
|---|
| Fussnoten: | Online verfügbar 16. September 2022, Artikelversion 4. Januar 2023 ; Gesehen am 06.06.2023 |
|---|
| Titel Quelle: | Enthalten in: Molecular therapy |
|---|
| Ort Quelle: | Amsterdam : Elsevier, 2000 |
|---|
| Jahr Quelle: | 2023 |
|---|
| Band/Heft Quelle: | 31(2023), 1 vom: Jan., Seite 282-299 |
|---|
| ISSN Quelle: | 1525-0024 |
|---|
| Abstract: | Huntington’s disease (HD) is a fatal neurodegenerative disorder with no effective cure currently available. Over the past few years our research has shown that alterations in sphingolipid metabolism represent a critical determinant in HD pathogenesis. In particular, aberrant metabolism of sphingosine-1-phosphate (S1P) has been reported in multiple disease settings, including human postmortem brains from HD patients. In this study, we investigate the potential therapeutic effect of the inhibition of S1P degradative enzyme SGPL1, by the chronic administration of the 2-acetyl-5-tetrahydroxybutyl imidazole (THI) inhibitor. We show that THI mitigated motor dysfunctions in both mouse and fly models of HD. The compound evoked the activation of pro-survival pathways, normalized levels of brain-derived neurotrophic factor, preserved white matter integrity, and stimulated synaptic functions in HD mice. Metabolically, THI restored normal levels of hexosylceramides and stimulated the autophagic and lysosomal machinery, facilitating the reduction of nuclear inclusions of both wild-type and mutant huntingtin proteins. |
|---|
| DOI: | doi:10.1016/j.ymthe.2022.09.004 |
|---|
| 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: https://doi.org/10.1016/j.ymthe.2022.09.004 |
|---|
| | Volltext: https://www.sciencedirect.com/science/article/pii/S1525001622005585 |
|---|
| | DOI: https://doi.org/10.1016/j.ymthe.2022.09.004 |
|---|
| Datenträger: | Online-Ressource |
|---|
| Sprache: | eng |
|---|
| Sach-SW: | glucosylceramide |
|---|
| | HD |
|---|
| | Htt |
|---|
| | neurodegeneration |
|---|
| | neuroprotection |
|---|
| | therapeutics |
|---|
| | THI |
|---|
| K10plus-PPN: | 1847490484 |
|---|
| Verknüpfungen: | → Zeitschrift |
|---|
Treatment with THI, an inhibitor of sphingosine-1-phosphate lyase, modulates glycosphingolipid metabolism and results therapeutically effective in experimental models of Huntington’s disease / Pepe, Giuseppe [VerfasserIn]; 4 January 2023 (Online-Ressource)
