Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

Qosa, Hisham; Miller, David S.; Pasinelli, Piera; Trotti, Davide

doi:10.1016/j.brainres.2015.07.005

Cited by 252Drug Transport and Resistance MechanismsBarrier Structure and Function StudiesPharmacogenetics and Drug Metabolism

Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

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Qosa, Hisham, Miller, David S., Pasinelli, Piera, Trotti, Davide·2015·Brain Research

DOI 10.1016/j.brainres.2015.07.005PMC PMC4681613

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Abstract

The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govern expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases. This article is part of a Special Issue entitled SI: Neuroprotection.

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ATP-binding cassette (ABC) transporters utilize ATP as an energy source and are primarily expressed at the luminal side of the blood-brain barrier endothelium.
“ATP-binding cassette (ABC) transporters utilize ATP as an energy source and are primarily expressed at the luminal side of the BBB endothelium (2, 488, 682).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [488]

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Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice
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Enhanced Brain Amyloid-β Clearance by Rifampicin and Caffeine as a Possible Protective Mechanism Against Alzheimer's Disease
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ABCB1, ABCG2, and PTEN Determine the Response of Glioblastoma to Temozolomide and ABT-888 Therapy
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Aβ1–42 reduces P-glycoprotein in the blood–brain barrier through RAGE–NF-κB signaling
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Brenn A Grube M Jedlitschky G Fischer A Strohmeier B Eiden M Keller M Groschup MH Vogelgesang S St. John's Wort reduces beta-amyloid accumulation in a double transgenic Alzheimer's disease mouse model-role of P-glycoprotein. Brain Pathol 2014 24 18 24 23701205 PMC8029238
You G Morris ME Overview of Drug Transporter Families. Drug Transporters: Molecular Characterization and Role in Drug Disposition 2006 1 10 John Wiley & Sons, Inc.

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Authors: Qosa, H., Miller, D. S., Pasinelli, P., & Trotti, D.
Affiliations: Thomas Jefferson University (US)
National Institutes of Health (US)
Corresponding author: Qosa, Hisham
Trotti, Davide
ORCID: Qosa, Hisham
Pasinelli, Piera
Trotti, Davide
Venue: Brain Research
Publisher: Elsevier BV
Published: 2015-12
Volume: 1628
Issue: Pt B
Pages: 298-316
ISSN: 0006-8993 (ISSN-L)
DOI: 10.1016/j.brainres.2015.07.005
PMC: PMC4681613
OpenAlex: W908901015
Cited by: 249
References: 215
Citations by year: 2026: 17 · 2025: 15 · 2024: 19 · 2023: 27 · 2022: 26 · 2021: 30 · 2020: 27 · 2019: 23 · 2018: 22 · 2017: 18 · 2016: 23 · 2015: 1 · 2012: 1
FWCI: 2.29
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Brain Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Health (RO1-NS074886)
Intramural Research program NIH/NIEHS
Topics: Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: ABC transporters, blood-brain barrier, P-glycoprotein, ABCG2, MRP1, MRP2, efflux pumps, transporter regulation, tight junctions, neurological disorders, neuroprotection, signaling pathways, brain capillary endothelium
MeSH terms: Animals, Blood-Brain Barrier, Humans, Nervous System Diseases, ATP-Binding Cassette Transporters

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Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders

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