Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease

Abstract Huntington’s disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is...

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Autores principales:	Alba Di Pardo, Enrico Amico, Abdul Basit, Andrea Armirotti, Piyush Joshi, M. Diana Neely, Romina Vuono, Salvatore Castaldo, Anna F. Digilio, Francesco Scalabrì, Giuseppe Pepe, Francesca Elifani, Michele Madonna, Se Kyoo Jeong, Bu-Mahn Park, Maurizio D’Esposito, Aaron B. Bowman, Roger A. Barker, Vittorio Maglione
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf0f9516edd7471585e05c6cc1d03c10
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spelling	oai:doaj.org-article:bf0f9516edd7471585e05c6cc1d03c102021-12-02T12:32:49ZDefective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease10.1038/s41598-017-05709-y2045-2322https://doaj.org/article/bf0f9516edd7471585e05c6cc1d03c102017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05709-yhttps://doaj.org/toc/2045-2322Abstract Huntington’s disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition.Alba Di PardoEnrico AmicoAbdul BasitAndrea ArmirottiPiyush JoshiM. Diana NeelyRomina VuonoSalvatore CastaldoAnna F. DigilioFrancesco ScalabrìGiuseppe PepeFrancesca ElifaniMichele MadonnaSe Kyoo JeongBu-Mahn ParkMaurizio D’EspositoAaron B. BowmanRoger A. BarkerVittorio MaglioneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alba Di Pardo Enrico Amico Abdul Basit Andrea Armirotti Piyush Joshi M. Diana Neely Romina Vuono Salvatore Castaldo Anna F. Digilio Francesco Scalabrì Giuseppe Pepe Francesca Elifani Michele Madonna Se Kyoo Jeong Bu-Mahn Park Maurizio D’Esposito Aaron B. Bowman Roger A. Barker Vittorio Maglione Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease
description	Abstract Huntington’s disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition.
format	article
author	Alba Di Pardo Enrico Amico Abdul Basit Andrea Armirotti Piyush Joshi M. Diana Neely Romina Vuono Salvatore Castaldo Anna F. Digilio Francesco Scalabrì Giuseppe Pepe Francesca Elifani Michele Madonna Se Kyoo Jeong Bu-Mahn Park Maurizio D’Esposito Aaron B. Bowman Roger A. Barker Vittorio Maglione
author_facet	Alba Di Pardo Enrico Amico Abdul Basit Andrea Armirotti Piyush Joshi M. Diana Neely Romina Vuono Salvatore Castaldo Anna F. Digilio Francesco Scalabrì Giuseppe Pepe Francesca Elifani Michele Madonna Se Kyoo Jeong Bu-Mahn Park Maurizio D’Esposito Aaron B. Bowman Roger A. Barker Vittorio Maglione
author_sort	Alba Di Pardo
title	Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease
title_short	Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease
title_full	Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease
title_fullStr	Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease
title_full_unstemmed	Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease
title_sort	defective sphingosine-1-phosphate metabolism is a druggable target in huntington’s disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bf0f9516edd7471585e05c6cc1d03c10
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Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington’s disease

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