Regulation of P-Glycoprotein in the Brain

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 subst...

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Bibliographic Details
Published in:International journal of molecular sciences 2022-11, Vol.23 (23), p.14667
Main Authors: Chai, Amanda B, Callaghan, Richard, Gelissen, Ingrid C
Format: Article
Language:English
Subjects:
Aging
Alzheimer's disease
ATP Binding Cassette Transporter, Subfamily B - metabolism
ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics
ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism
Blood-brain barrier
Blood-Brain Barrier - metabolism
Brain - metabolism
Central Nervous System Agents
Convulsions & seizures
Drug resistance
Endothelial cells
Endothelial Cells - metabolism
Glycoproteins
Kinases
Ligands
Neurotoxicity
Oxidative stress
P-Glycoprotein
Peptides
Pharmacokinetics
Post-transcription
Post-translation
Protein expression
Proteins
Review
Transcription factors
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms232314667