Chai, AB, Callaghan, R orcid.org/0000-0001-6136-3532 and Gelissen, IC (2022) Regulation of P-Glycoprotein in the Brain. International Journal of Molecular Sciences, 23 (23). 14667. ISSN 1661-6596
Abstract
Maintenance of the tightly regulated homeostatic environment of the brain is facilitated by the blood–brain barrier (BBB). P-glycoprotein (P-gp), an ATP-binding cassette transporter, is expressed on the luminal surface of the endothelial cells in the BBB, and actively exports a wide variety of substrates to limit exposure of the vulnerable brain environment to waste buildup and neurotoxic compounds. Downregulation of P-gp expression and activity at the BBB have been reported with ageing and in neurodegenerative diseases. Upregulation of P-gp at the BBB contributes to poor therapeutic outcomes due to altered pharmacokinetics of CNS-acting drugs. The regulation of P-gp is highly complex, but unravelling the mechanisms involved may help the development of novel and nuanced strategies to modulate P-gp expression for therapeutic benefit. This review summarises the current understanding of P-gp regulation in the brain, encompassing the transcriptional, post-transcriptional and post-translational mechanisms that have been identified to affect P-gp expression and transport activity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | P-glycoprotein; ABCB1; blood–brain barrier; transcriptional regulation; post-transcriptional regulation; post-translational regulation |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Feb 2023 12:48 |
Last Modified: | 20 Feb 2023 12:48 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/ijms232314667 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:196331 |
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