Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level
The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removin...
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doaj-9000b66328e24821ae29e38d264ebacb2021-04-03T23:01:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01223742374210.3390/ijms22073742Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier LevelSweilem B. Al Rihani0Lucy I. Darakjian1Malavika Deodhar2Pamela Dow3Jacques Turgeon4Veronique Michaud5Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USATabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USAThe blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies. Pathophysiological stressors, age, and age-associated disorders may alter the expression level and functionality of transporter protein elements that modulate drug distribution and accumulation into the brain, namely, drug efficacy and toxicity. This review focuses and sheds light on the influence of inflammatory conditions and diseases such as Alzheimer’s disease, epilepsy, and stroke on the expression and functionality of the BBB drug transporters, the consequential modulation of drug distribution to the brain, and their impact on drug efficacy and toxicity.https://www.mdpi.com/1422-0067/22/7/3742the blood–brain barrierdrug transportersAlzheimer’s diseasestrokeepilepsyneuroinflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sweilem B. Al Rihani Lucy I. Darakjian Malavika Deodhar Pamela Dow Jacques Turgeon Veronique Michaud |
spellingShingle |
Sweilem B. Al Rihani Lucy I. Darakjian Malavika Deodhar Pamela Dow Jacques Turgeon Veronique Michaud Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level International Journal of Molecular Sciences the blood–brain barrier drug transporters Alzheimer’s disease stroke epilepsy neuroinflammation |
author_facet |
Sweilem B. Al Rihani Lucy I. Darakjian Malavika Deodhar Pamela Dow Jacques Turgeon Veronique Michaud |
author_sort |
Sweilem B. Al Rihani |
title |
Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level |
title_short |
Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level |
title_full |
Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level |
title_fullStr |
Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level |
title_full_unstemmed |
Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level |
title_sort |
disease-induced modulation of drug transporters at the blood–brain barrier level |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-04-01 |
description |
The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies. Pathophysiological stressors, age, and age-associated disorders may alter the expression level and functionality of transporter protein elements that modulate drug distribution and accumulation into the brain, namely, drug efficacy and toxicity. This review focuses and sheds light on the influence of inflammatory conditions and diseases such as Alzheimer’s disease, epilepsy, and stroke on the expression and functionality of the BBB drug transporters, the consequential modulation of drug distribution to the brain, and their impact on drug efficacy and toxicity. |
topic |
the blood–brain barrier drug transporters Alzheimer’s disease stroke epilepsy neuroinflammation |
url |
https://www.mdpi.com/1422-0067/22/7/3742 |
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