Multiple Sclerosis and the Blood-Central Nervous System Barrier

The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit...

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Autor principal: Palmer, Alan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562587/
https://www.ncbi.nlm.nih.gov/pubmed/23401746
http://dx.doi.org/10.1155/2013/530356
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author Palmer, Alan M.
author_facet Palmer, Alan M.
author_sort Palmer, Alan M.
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description The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit their movement across the BCNSB and into the CNS. Once there, these immune cells target particular self-epitopes and initiate a cascade of neuroinflammation, which leads to the breakdown of the BCNSB and the formation of perivascular plaques, one of the hallmarks of MS. Immunomodulatory drugs for MS are either biologics or small molecules, with only the latter having the capacity to cross the BCNSB and thus have a propensity to cause CNS side effects. However, BCNSB penetration is a desirable feature of MS drugs that have molecular targets within the CNS. These are nabiximols and dalfampridine, which target cannabinoid receptors and potassium channels, respectively. Vascular cell adhesion molecule-1, present on endothelial cells of the BCNSB, also serves as a drug discovery target since it interacts with α4-β1-integrin on leucocytes. The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS.
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spelling pubmed-35625872013-02-11 Multiple Sclerosis and the Blood-Central Nervous System Barrier Palmer, Alan M. Cardiovasc Psychiatry Neurol Review Article The central nervous system (CNS) is isolated from the blood system by a physical barrier that contains efflux transporters and catabolic enzymes. This blood-CNS barrier (BCNSB) plays a pivotal role in the pathophysiology of multiple sclerosis (MS). It binds and anchors activated leukocytes to permit their movement across the BCNSB and into the CNS. Once there, these immune cells target particular self-epitopes and initiate a cascade of neuroinflammation, which leads to the breakdown of the BCNSB and the formation of perivascular plaques, one of the hallmarks of MS. Immunomodulatory drugs for MS are either biologics or small molecules, with only the latter having the capacity to cross the BCNSB and thus have a propensity to cause CNS side effects. However, BCNSB penetration is a desirable feature of MS drugs that have molecular targets within the CNS. These are nabiximols and dalfampridine, which target cannabinoid receptors and potassium channels, respectively. Vascular cell adhesion molecule-1, present on endothelial cells of the BCNSB, also serves as a drug discovery target since it interacts with α4-β1-integrin on leucocytes. The MS drug natalizumab, a humanized monoclonal antibody against α4-β1-integrin, blocks this interaction and thus reduces the movement of immune cells into the CNS. This paper further elaborates on the role of the BCNSB in the pathophysiology and pharmacotherapy of MS. Hindawi Publishing Corporation 2013 2013-01-15 /pmc/articles/PMC3562587/ /pubmed/23401746 http://dx.doi.org/10.1155/2013/530356 Text en Copyright © 2013 Alan M. Palmer. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Palmer, Alan M.
Multiple Sclerosis and the Blood-Central Nervous System Barrier
title Multiple Sclerosis and the Blood-Central Nervous System Barrier
title_full Multiple Sclerosis and the Blood-Central Nervous System Barrier
title_fullStr Multiple Sclerosis and the Blood-Central Nervous System Barrier
title_full_unstemmed Multiple Sclerosis and the Blood-Central Nervous System Barrier
title_short Multiple Sclerosis and the Blood-Central Nervous System Barrier
title_sort multiple sclerosis and the blood-central nervous system barrier
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562587/
https://www.ncbi.nlm.nih.gov/pubmed/23401746
http://dx.doi.org/10.1155/2013/530356
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