Functional expression of drug transporters in glial cells: potential role on drug delivery to the CNS
- PMID: 25307214
- DOI: 10.1016/bs.apha.2014.06.010
Functional expression of drug transporters in glial cells: potential role on drug delivery to the CNS
Abstract
Drug permeability in the central nervous system (CNS) across blood-brain and blood-cerebrospinal fluid barriers is an important determinant of neurological disorders therapeutic efficacy and is highly regulated by the expression of membrane-associated transporters belonging to the ATP-binding cassette (ABC) and solute carrier (SLC) superfamilies. Functional expression of ABC efflux transporters exists not only at the brain barriers (primary biochemical barrier) but also in astrocytes, microglia, neurons, and oligodendrocytes can significantly restrict drug penetration into these cells, thus creating a secondary biochemical barrier to permeability in brain parenchyma. In contrast, SLC members primarily contribute to the uptake of endogenous substrates (i.e., hormones, neurotransmitters) and pharmacological agents and can play a critical role in maintaining CNS homeostasis and drug response. In this chapter, we review the functional expression and localization of drug transporters in the brain, their role in CNS drug delivery, and their regulation in neuropathological conditions.
Keywords: ABC transporters; Brain barriers; Brain drug permeability; Brain parenchyma; Neurological disorders; SLC transporters; Transporter regulation.
© 2014 Elsevier Inc. All rights reserved.
Similar articles
-
Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations.Pharmacol Rev. 2001 Dec;53(4):569-96. Pharmacol Rev. 2001. PMID: 11734619 Review.
-
Membrane transporter proteins: a challenge for CNS drug development.Dialogues Clin Neurosci. 2006;8(3):311-21. doi: 10.31887/DCNS.2006.8.3/fgirardin. Dialogues Clin Neurosci. 2006. PMID: 17117613 Free PMC article. Review.
-
[Multi-disciplinary research approaches on the brain barrier transport system, a dynamic interface].Brain Nerve. 2013 Feb;65(2):121-36. Brain Nerve. 2013. PMID: 23399670 Review. Japanese.
-
Regulation of ABC membrane transporters in glial cells: relevance to the pharmacotherapy of brain HIV-1 infection.Glia. 2008 Dec;56(16):1711-35. doi: 10.1002/glia.20725. Glia. 2008. PMID: 18649402 Review.
-
Role of nuclear receptors in the regulation of drug transporters in the brain.Trends Pharmacol Sci. 2013 Jul;34(7):361-72. doi: 10.1016/j.tips.2013.05.004. Epub 2013 Jun 13. Trends Pharmacol Sci. 2013. PMID: 23769624 Review.
Cited by
-
Astrocytes drive upregulation of the multidrug resistance transporter ABCB1 (P-Glycoprotein) in endothelial cells of the blood-brain barrier in mutant superoxide dismutase 1-linked amyotrophic lateral sclerosis.Glia. 2016 Aug;64(8):1298-313. doi: 10.1002/glia.23003. Epub 2016 May 9. Glia. 2016. PMID: 27158936 Free PMC article.
-
Drug Transporters at the Human Blood-Testis Barrier.Drug Metab Dispos. 2023 May;51(5):560-571. doi: 10.1124/dmd.122.001186. Epub 2023 Feb 2. Drug Metab Dispos. 2023. PMID: 36732077 Free PMC article. Review.
-
The solute carrier transporters and the brain: Physiological and pharmacological implications.Asian J Pharm Sci. 2020 Mar;15(2):131-144. doi: 10.1016/j.ajps.2019.09.002. Epub 2019 Nov 13. Asian J Pharm Sci. 2020. PMID: 32373195 Free PMC article. Review.
-
Regulation of ABC Drug Efflux Transporters in Human T-Cells Exposed to an HIV Pseudotype.Front Pharmacol. 2021 Aug 4;12:711999. doi: 10.3389/fphar.2021.711999. eCollection 2021. Front Pharmacol. 2021. PMID: 34421607 Free PMC article.
-
Novel localization of folate transport systems in the murine central nervous system.Fluids Barriers CNS. 2022 Nov 23;19(1):92. doi: 10.1186/s12987-022-00391-3. Fluids Barriers CNS. 2022. PMID: 36419095 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
