Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview

The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity is vital to maintain the homeostasis of the brain microenvironment by controlling the passage of substances and regulating the trafficking of immune cells between the...

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Autores principales: Sabrina Rahman Archie, Abdullah Al Shoyaib, Luca Cucullo
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/214b7b31b1784a94bc2eb0196fcad770
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spelling oai:doaj.org-article:214b7b31b1784a94bc2eb0196fcad7702021-11-25T18:40:40ZBlood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview10.3390/pharmaceutics131117791999-4923https://doaj.org/article/214b7b31b1784a94bc2eb0196fcad7702021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1779https://doaj.org/toc/1999-4923The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity is vital to maintain the homeostasis of the brain microenvironment by controlling the passage of substances and regulating the trafficking of immune cells between the blood and the brain. The BBB is primarily composed of highly specialized microvascular endothelial cells. These cells’ special features and physiological properties are acquired and maintained through the concerted effort of hemodynamic and cellular cues from the surrounding environment. This complex multicellular system, comprising endothelial cells, astrocytes, pericytes, and neurons, is known as the neurovascular unit (NVU). The BBB strictly controls the transport of nutrients and metabolites into brain parenchyma through a tightly regulated transport system while limiting the access of potentially harmful substances via efflux transcytosis and metabolic mechanisms. Not surprisingly, a disruption of the BBB has been associated with the onset and/or progression of major neurological disorders. Although the association between disease and BBB disruption is clear, its nature is not always evident, specifically with regard to whether an impaired BBB function results from the pathological condition or whether the BBB damage is the primary pathogenic factor prodromal to the onset of the disease. In either case, repairing the barrier could be a viable option for treating and/or reducing the effects of CNS disorders. In this review, we describe the fundamental structure and function of the BBB in both healthy and altered/diseased conditions. Additionally, we provide an overview of the potential therapeutic targets that could be leveraged to restore the integrity of the BBB concomitant to the treatment of these brain disorders.Sabrina Rahman ArchieAbdullah Al ShoyaibLuca CuculloMDPI AGarticlebiological barrierstight junctionsendothelialdysfunctionstrokeviabilityPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1779, p 1779 (2021)
institution DOAJ
collection DOAJ
language EN
topic biological barriers
tight junctions
endothelial
dysfunction
stroke
viability
Pharmacy and materia medica
RS1-441
spellingShingle biological barriers
tight junctions
endothelial
dysfunction
stroke
viability
Pharmacy and materia medica
RS1-441
Sabrina Rahman Archie
Abdullah Al Shoyaib
Luca Cucullo
Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
description The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity is vital to maintain the homeostasis of the brain microenvironment by controlling the passage of substances and regulating the trafficking of immune cells between the blood and the brain. The BBB is primarily composed of highly specialized microvascular endothelial cells. These cells’ special features and physiological properties are acquired and maintained through the concerted effort of hemodynamic and cellular cues from the surrounding environment. This complex multicellular system, comprising endothelial cells, astrocytes, pericytes, and neurons, is known as the neurovascular unit (NVU). The BBB strictly controls the transport of nutrients and metabolites into brain parenchyma through a tightly regulated transport system while limiting the access of potentially harmful substances via efflux transcytosis and metabolic mechanisms. Not surprisingly, a disruption of the BBB has been associated with the onset and/or progression of major neurological disorders. Although the association between disease and BBB disruption is clear, its nature is not always evident, specifically with regard to whether an impaired BBB function results from the pathological condition or whether the BBB damage is the primary pathogenic factor prodromal to the onset of the disease. In either case, repairing the barrier could be a viable option for treating and/or reducing the effects of CNS disorders. In this review, we describe the fundamental structure and function of the BBB in both healthy and altered/diseased conditions. Additionally, we provide an overview of the potential therapeutic targets that could be leveraged to restore the integrity of the BBB concomitant to the treatment of these brain disorders.
format article
author Sabrina Rahman Archie
Abdullah Al Shoyaib
Luca Cucullo
author_facet Sabrina Rahman Archie
Abdullah Al Shoyaib
Luca Cucullo
author_sort Sabrina Rahman Archie
title Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
title_short Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
title_full Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
title_fullStr Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
title_full_unstemmed Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
title_sort blood-brain barrier dysfunction in cns disorders and putative therapeutic targets: an overview
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/214b7b31b1784a94bc2eb0196fcad770
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AT abdullahalshoyaib bloodbrainbarrierdysfunctionincnsdisordersandputativetherapeutictargetsanoverview
AT lucacucullo bloodbrainbarrierdysfunctionincnsdisordersandputativetherapeutictargetsanoverview
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