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Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration

Sphingosine-1-phosphate lyase (SPL) is a pyridoxal 5′-phosphate-dependent enzyme involved in the irreversible degradation of sphingosine-1-phosphate (S1P)—a bioactive sphingolipid that modulates a broad range of biological processes (cell proliferation, migration, differentiation and survival; mitoc...

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Autores principales: Wieczorek, Iga, Strosznajder, Robert Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093903/
https://www.ncbi.nlm.nih.gov/pubmed/37047151
http://dx.doi.org/10.3390/ijms24076180
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author Wieczorek, Iga
Strosznajder, Robert Piotr
author_facet Wieczorek, Iga
Strosznajder, Robert Piotr
author_sort Wieczorek, Iga
collection PubMed
description Sphingosine-1-phosphate lyase (SPL) is a pyridoxal 5′-phosphate-dependent enzyme involved in the irreversible degradation of sphingosine-1-phosphate (S1P)—a bioactive sphingolipid that modulates a broad range of biological processes (cell proliferation, migration, differentiation and survival; mitochondrial functioning; and gene expression). Although SPL activity leads to a decrease in the available pool of S1P in the cell, at the same time, hexadecenal and phosphoethanolamine, compounds with potential biological activity, are generated. The increased expression and/or activity of SPL, and hence the imbalance between S1P and the end products of its cleavage, were demonstrated in several pathological states. On the other hand, loss-of-function mutations in the SPL encoding gene are a cause of severe developmental impairments. Recently, special attention has been paid to neurodegenerative diseases as the most common pathologies of the nervous system. This review summarizes the current findings concerning the role of SPL in the nervous system with an emphasis on neurodegeneration. Moreover, it briefly discusses pharmacological compounds directed to inhibit its activity.
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spelling pubmed-100939032023-04-13 Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration Wieczorek, Iga Strosznajder, Robert Piotr Int J Mol Sci Review Sphingosine-1-phosphate lyase (SPL) is a pyridoxal 5′-phosphate-dependent enzyme involved in the irreversible degradation of sphingosine-1-phosphate (S1P)—a bioactive sphingolipid that modulates a broad range of biological processes (cell proliferation, migration, differentiation and survival; mitochondrial functioning; and gene expression). Although SPL activity leads to a decrease in the available pool of S1P in the cell, at the same time, hexadecenal and phosphoethanolamine, compounds with potential biological activity, are generated. The increased expression and/or activity of SPL, and hence the imbalance between S1P and the end products of its cleavage, were demonstrated in several pathological states. On the other hand, loss-of-function mutations in the SPL encoding gene are a cause of severe developmental impairments. Recently, special attention has been paid to neurodegenerative diseases as the most common pathologies of the nervous system. This review summarizes the current findings concerning the role of SPL in the nervous system with an emphasis on neurodegeneration. Moreover, it briefly discusses pharmacological compounds directed to inhibit its activity. MDPI 2023-03-24 /pmc/articles/PMC10093903/ /pubmed/37047151 http://dx.doi.org/10.3390/ijms24076180 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wieczorek, Iga
Strosznajder, Robert Piotr
Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration
title Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration
title_full Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration
title_fullStr Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration
title_full_unstemmed Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration
title_short Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration
title_sort recent insight into the role of sphingosine-1-phosphate lyase in neurodegeneration
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10093903/
https://www.ncbi.nlm.nih.gov/pubmed/37047151
http://dx.doi.org/10.3390/ijms24076180
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