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Adenosine receptor signaling: a key to opening the blood–brain door
The aim of this review is to outline evidence that adenosine receptor (AR) activation can modulate blood–brain barrier (BBB) permeability and the implications for disease states and drug delivery. Barriers of the central nervous system (CNS) constitute a protective and regulatory interface between t...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557218/ https://www.ncbi.nlm.nih.gov/pubmed/26330053 http://dx.doi.org/10.1186/s12987-015-0017-7 |
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author | Bynoe, Margaret S. Viret, Christophe Yan, Angela Kim, Do-Geun |
author_facet | Bynoe, Margaret S. Viret, Christophe Yan, Angela Kim, Do-Geun |
author_sort | Bynoe, Margaret S. |
collection | PubMed |
description | The aim of this review is to outline evidence that adenosine receptor (AR) activation can modulate blood–brain barrier (BBB) permeability and the implications for disease states and drug delivery. Barriers of the central nervous system (CNS) constitute a protective and regulatory interface between the CNS and the rest of the organism. Such barriers allow for the maintenance of the homeostasis of the CNS milieu. Among them, the BBB is a highly efficient permeability barrier that separates the brain micro-environment from the circulating blood. It is made up of tight junction-connected endothelial cells with specialized transporters to selectively control the passage of nutrients required for neural homeostasis and function, while preventing the entry of neurotoxic factors. The identification of cellular and molecular mechanisms involved in the development and function of CNS barriers is required for a better understanding of CNS homeostasis in both physiological and pathological settings. It has long been recognized that the endogenous purine nucleoside adenosine is a potent modulator of a large number of neurological functions. More recently, experimental studies conducted with human/mouse brain primary endothelial cells as well as with mouse models, indicate that adenosine markedly regulates BBB permeability. Extracellular adenosine, which is efficiently generated through the catabolism of ATP via the CD39/CD73 ecto-nucleotidase axis, promotes BBB permeability by signaling through A(1) and A(2A) ARs expressed on BBB cells. In line with this hypothesis, induction of AR signaling by selective agonists efficiently augments BBB permeability in a transient manner and promotes the entry of macromolecules into the CNS. Conversely, antagonism of AR signaling blocks the entry of inflammatory cells and soluble factors into the brain. Thus, AR modulation of the BBB appears as a system susceptible to tighten as well as to permeabilize the BBB. Collectively, these findings point to AR manipulation as a pertinent avenue of research for novel strategies aiming at efficiently delivering therapeutic drugs/cells into the CNS, or at restricting the entry of inflammatory immune cells into the brain in some diseases such as multiple sclerosis. |
format | Online Article Text |
id | pubmed-4557218 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45572182015-09-03 Adenosine receptor signaling: a key to opening the blood–brain door Bynoe, Margaret S. Viret, Christophe Yan, Angela Kim, Do-Geun Fluids Barriers CNS Review The aim of this review is to outline evidence that adenosine receptor (AR) activation can modulate blood–brain barrier (BBB) permeability and the implications for disease states and drug delivery. Barriers of the central nervous system (CNS) constitute a protective and regulatory interface between the CNS and the rest of the organism. Such barriers allow for the maintenance of the homeostasis of the CNS milieu. Among them, the BBB is a highly efficient permeability barrier that separates the brain micro-environment from the circulating blood. It is made up of tight junction-connected endothelial cells with specialized transporters to selectively control the passage of nutrients required for neural homeostasis and function, while preventing the entry of neurotoxic factors. The identification of cellular and molecular mechanisms involved in the development and function of CNS barriers is required for a better understanding of CNS homeostasis in both physiological and pathological settings. It has long been recognized that the endogenous purine nucleoside adenosine is a potent modulator of a large number of neurological functions. More recently, experimental studies conducted with human/mouse brain primary endothelial cells as well as with mouse models, indicate that adenosine markedly regulates BBB permeability. Extracellular adenosine, which is efficiently generated through the catabolism of ATP via the CD39/CD73 ecto-nucleotidase axis, promotes BBB permeability by signaling through A(1) and A(2A) ARs expressed on BBB cells. In line with this hypothesis, induction of AR signaling by selective agonists efficiently augments BBB permeability in a transient manner and promotes the entry of macromolecules into the CNS. Conversely, antagonism of AR signaling blocks the entry of inflammatory cells and soluble factors into the brain. Thus, AR modulation of the BBB appears as a system susceptible to tighten as well as to permeabilize the BBB. Collectively, these findings point to AR manipulation as a pertinent avenue of research for novel strategies aiming at efficiently delivering therapeutic drugs/cells into the CNS, or at restricting the entry of inflammatory immune cells into the brain in some diseases such as multiple sclerosis. BioMed Central 2015-09-02 /pmc/articles/PMC4557218/ /pubmed/26330053 http://dx.doi.org/10.1186/s12987-015-0017-7 Text en © Bynoe et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Bynoe, Margaret S. Viret, Christophe Yan, Angela Kim, Do-Geun Adenosine receptor signaling: a key to opening the blood–brain door |
title | Adenosine receptor signaling: a key to opening the blood–brain door |
title_full | Adenosine receptor signaling: a key to opening the blood–brain door |
title_fullStr | Adenosine receptor signaling: a key to opening the blood–brain door |
title_full_unstemmed | Adenosine receptor signaling: a key to opening the blood–brain door |
title_short | Adenosine receptor signaling: a key to opening the blood–brain door |
title_sort | adenosine receptor signaling: a key to opening the blood–brain door |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557218/ https://www.ncbi.nlm.nih.gov/pubmed/26330053 http://dx.doi.org/10.1186/s12987-015-0017-7 |
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