Abstract
In the blood–brain barrier several ABC transporters are expressed at the luminal, blood-facing, plasma membrane of the brain capillary endothelial cells. There they function as ATP-driven efflux pumps for xenobiotics and endogenous metabolites, thus providing an important element of the barrier. When these transporters limit neurotoxicant entry into the CNS, they are neuroprotective; when they limit therapeutic drug entry, they become major obstacles to drug delivery to treat CNS diseases. Here I review function and regulation of ABC transporters at the blood–brain barrier, with an emphasis on recently disclosed mechanisms that alter transporter expression and transport activity.
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Abbreviations
- ABC:
-
ATP-binding cassette
- AD:
-
Alzheimer’s disease
- AEDs:
-
Antiepileptic drugs
- AhR:
-
Arylhydrocarbon receptor
- Akt:
-
Protein kinase B
- ApoE:
-
Apolipoprotein E
- BCRP:
-
Breast cancer resistance protein (ABCG2)
- BSEP:
-
Bile salt export pump
- CAR:
-
Constitutive androstane receptor
- CFTR:
-
Cystic fibrosis transmembrane regulator (ABCC7)
- CNS:
-
Central nervous system
- COX-2:
-
Cyclo-oxygenase-2
- E2:
-
17-β-estradiol
- EP-1:
-
Prostaglandin E2 receptor
- ER:
-
Estrogen receptor
- FXR:
-
Farnesyl-X receptor
- GSK-3β:
-
Glycogen synthase kinase 3 beta
- hAPP:
-
Human amyloid precursor protein
- iNOS:
-
Inducible nitric oxide synthase
- JNK:
-
c-Jun N-terminal kinase
- LXR:
-
Liver-X receptor
- MRP:
-
Multidrug resistance-associated protein
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NMDA:
-
N-methyl-d-aspartate
- PCBs:
-
Polychlorinated biphenyls
- PCN:
-
Pregnenolone-16-alpha-carbonitrile
- PCR:
-
Polymerase chain reaction
- PI3-K:
-
Phosphatidylinositide 3-kinase
- PK:
-
Pharmacokinetics
- PKCβ1:
-
Protein kinase C isoform β1
- PTEN:
-
Phosphatase and tensin homolog
- PXR:
-
Pregnane-X receptor
- S1P:
-
Sphingosine-1-phosphate
- S1PR1:
-
Sphingosine-1-phosphate receptor 1
- TNF-α:
-
Tumor necrosis factor-α
- VDR:
-
Vitamin D receptor
- VEGF:
-
Vascular endothelial growth factor
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Acknowledgements
This work was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. I thank all the past and present members of my laboratory for their hard work and creativity.
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Miller, D.S. (2013). ABC Transporters at the Blood–Brain Barrier. In: Fricker, G., Ott, M., Mahringer, A. (eds) The Blood Brain Barrier (BBB). Topics in Medicinal Chemistry, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2013_31
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