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A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis
Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain. Impairments in the process of myelination, or demyelinating insults, might cause chronic diseases such as multiple sclerosis (MS). Under physiological conditions, remyelination is an ongoing process throughout adult...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202686/ https://www.ncbi.nlm.nih.gov/pubmed/34135730 http://dx.doi.org/10.3389/fnins.2021.677988 |
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author | Coppi, Elisabetta Cencetti, Francesca Cherchi, Federica Venturini, Martina Donati, Chiara Bruni, Paola Pedata, Felicita Pugliese, Anna Maria |
author_facet | Coppi, Elisabetta Cencetti, Francesca Cherchi, Federica Venturini, Martina Donati, Chiara Bruni, Paola Pedata, Felicita Pugliese, Anna Maria |
author_sort | Coppi, Elisabetta |
collection | PubMed |
description | Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain. Impairments in the process of myelination, or demyelinating insults, might cause chronic diseases such as multiple sclerosis (MS). Under physiological conditions, remyelination is an ongoing process throughout adult life consisting in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes (OLs). During pathological events, this process fails due to unfavorable environment. Adenosine and sphingosine kinase/sphingosine 1-phosphate signaling axes (SphK/S1P) play important roles in remyelination processes. Remarkably, fingolimod (FTY720), a sphingosine analog recently approved for MS treatment, plays important roles in OPC maturation. We recently demonstrated that the selective stimulation of A(2)(B) adenosine receptors (A(2)(B)Rs) inhibit OPC differentiation in vitro and reduce voltage-dependent outward K(+) currents (I(K)) necessary to OPC maturation, whereas specific SphK1 or SphK2 inhibition exerts the opposite effect. During OPC differentiation A(2)(B)R expression increases, this effect being prevented by SphK1/2 blockade. Furthermore, selective silencing of A(2)(B)R in OPC cultures prompts maturation and, intriguingly, enhances the expression of S1P lyase, the enzyme responsible for irreversible S1P catabolism. Finally, the existence of an interplay between SphK1/S1P pathway and A(2)(B)Rs in OPCs was confirmed since acute stimulation of A(2)(B)Rs activates SphK1 by increasing its phosphorylation. Here the role of A(2)(B)R and SphK/S1P signaling during oligodendrogenesis is reviewed in detail, with the purpose to shed new light on the interaction between A(2)(B)Rs and S1P signaling, as eventual innovative targets for the treatment of demyelinating disorders. |
format | Online Article Text |
id | pubmed-8202686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82026862021-06-15 A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis Coppi, Elisabetta Cencetti, Francesca Cherchi, Federica Venturini, Martina Donati, Chiara Bruni, Paola Pedata, Felicita Pugliese, Anna Maria Front Neurosci Neuroscience Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain. Impairments in the process of myelination, or demyelinating insults, might cause chronic diseases such as multiple sclerosis (MS). Under physiological conditions, remyelination is an ongoing process throughout adult life consisting in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes (OLs). During pathological events, this process fails due to unfavorable environment. Adenosine and sphingosine kinase/sphingosine 1-phosphate signaling axes (SphK/S1P) play important roles in remyelination processes. Remarkably, fingolimod (FTY720), a sphingosine analog recently approved for MS treatment, plays important roles in OPC maturation. We recently demonstrated that the selective stimulation of A(2)(B) adenosine receptors (A(2)(B)Rs) inhibit OPC differentiation in vitro and reduce voltage-dependent outward K(+) currents (I(K)) necessary to OPC maturation, whereas specific SphK1 or SphK2 inhibition exerts the opposite effect. During OPC differentiation A(2)(B)R expression increases, this effect being prevented by SphK1/2 blockade. Furthermore, selective silencing of A(2)(B)R in OPC cultures prompts maturation and, intriguingly, enhances the expression of S1P lyase, the enzyme responsible for irreversible S1P catabolism. Finally, the existence of an interplay between SphK1/S1P pathway and A(2)(B)Rs in OPCs was confirmed since acute stimulation of A(2)(B)Rs activates SphK1 by increasing its phosphorylation. Here the role of A(2)(B)R and SphK/S1P signaling during oligodendrogenesis is reviewed in detail, with the purpose to shed new light on the interaction between A(2)(B)Rs and S1P signaling, as eventual innovative targets for the treatment of demyelinating disorders. Frontiers Media S.A. 2021-05-26 /pmc/articles/PMC8202686/ /pubmed/34135730 http://dx.doi.org/10.3389/fnins.2021.677988 Text en Copyright © 2021 Coppi, Cencetti, Cherchi, Venturini, Donati, Bruni, Pedata and Pugliese. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Coppi, Elisabetta Cencetti, Francesca Cherchi, Federica Venturini, Martina Donati, Chiara Bruni, Paola Pedata, Felicita Pugliese, Anna Maria A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis |
title | A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis |
title_full | A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis |
title_fullStr | A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis |
title_full_unstemmed | A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis |
title_short | A(2)(B) Adenosine Receptors and Sphingosine 1-Phosphate Signaling Cross-Talk in Oligodendrogliogenesis |
title_sort | a(2)(b) adenosine receptors and sphingosine 1-phosphate signaling cross-talk in oligodendrogliogenesis |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202686/ https://www.ncbi.nlm.nih.gov/pubmed/34135730 http://dx.doi.org/10.3389/fnins.2021.677988 |
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