Abstract
At the blood-brain barrier, ATP-binding cassette (ABC) transporters, such as, P-glycoprotein (MDR1, ABCB1) and breast cancer related protein (BCRP, ABCG2) limit CNS uptake of foreign chemicals. Thus, they are neuroprotective, but they also distinguish poorly between neurotoxicants and therapeutic drugs. So they are major obstacles to CNS pharmacotherapy. The present review is focused on new findings in animal models in vitro and in vivo showing that basal transport activity of P-glycoprotein and Bcrp can be rapidly and transiently reduced through targeting of specific signaling pathways within the brain capillary endothelium. Three pathways have been identified: estrogen signaling to Bcrp, vascular endothelial growth factor signaling to P-glycoprotein and TNFα/PKC/ sphingolipid signaling to P-glycoprotein. Translation of these results to the clinic could provide improved pharmacotherapy for a number of CNS diseases, including, brain cancer, neuroAIDS and epilepsy.
Keywords: Neuroprotection, Drug delivery, ABC transporters, Blood-brain barrier, P-gp, efflux pumps.
Current Pharmaceutical Design
Title:Signaling Pathways that Regulate Basal ABC Transporter Activity at the Blood- Brain Barrier
Volume: 20 Issue: 10
Author(s): David S. Miller and Ronald E. Cannon
Affiliation:
Keywords: Neuroprotection, Drug delivery, ABC transporters, Blood-brain barrier, P-gp, efflux pumps.
Abstract: At the blood-brain barrier, ATP-binding cassette (ABC) transporters, such as, P-glycoprotein (MDR1, ABCB1) and breast cancer related protein (BCRP, ABCG2) limit CNS uptake of foreign chemicals. Thus, they are neuroprotective, but they also distinguish poorly between neurotoxicants and therapeutic drugs. So they are major obstacles to CNS pharmacotherapy. The present review is focused on new findings in animal models in vitro and in vivo showing that basal transport activity of P-glycoprotein and Bcrp can be rapidly and transiently reduced through targeting of specific signaling pathways within the brain capillary endothelium. Three pathways have been identified: estrogen signaling to Bcrp, vascular endothelial growth factor signaling to P-glycoprotein and TNFα/PKC/ sphingolipid signaling to P-glycoprotein. Translation of these results to the clinic could provide improved pharmacotherapy for a number of CNS diseases, including, brain cancer, neuroAIDS and epilepsy.
Export Options
About this article
Cite this article as:
Miller S. David and Cannon E. Ronald, Signaling Pathways that Regulate Basal ABC Transporter Activity at the Blood- Brain Barrier, Current Pharmaceutical Design 2014; 20 (10) . https://dx.doi.org/10.2174/13816128113199990457
DOI https://dx.doi.org/10.2174/13816128113199990457 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Advances in Neuroimaging for HIV-1 Associated Neurological Dysfunction: Clues to the Diagnosis, Pathogenesis and Therapeutic Monitoring
Current HIV Research Bispidine as a Privileged Scaffold
Current Topics in Medicinal Chemistry Role of Adenosine Kinase Inhibitor in Adenosine Augmentation Therapy for Epilepsy: A Potential Novel Drug for Epilepsy
Current Drug Targets Cardiovascular Toxicity from the Perspective of Oxidative Stress, Electron Transfer, and Prevention by Antioxidants
Current Vascular Pharmacology Involvement of Cannabinoids in Cellular Proliferation
Mini-Reviews in Medicinal Chemistry Neurotrophic and Neuroprotective Effects of Muscle Contraction
Current Pharmaceutical Design Nose-to-Brain Drug Delivery by Nanoparticles in the Treatment of Neurological Disorders
Current Medicinal Chemistry Chemical Biology of mGlu4 Receptor Activation: Dogmas, Challenges, Strategies and Opportunities
Current Topics in Medicinal Chemistry The Therapeutic Applications of Exosomes in Different Types of Diseases: A Review
Current Molecular Medicine Medicinal Chemistry of Potassium Channel Modulators: An Update of Recent Progress (2011-2017)
Current Medicinal Chemistry Pharmacophore Identification and Quantitative Bioactivity Prediction Using the Electron-Conformational Method
Current Pharmaceutical Design Editorial [Abnormal Bleeding or Bruising Associated with Antiepileptic Treatment]
Current Drug Safety Cognitive Identity in Schizophrenia: Vision, Space, and Body Perception from Prodrome to Syndrome
Current Psychiatry Reviews Age-Specific Impairment of Morris Water Maze Performance Following Neonatal Exposure to Magnetic Resonance Image in Rats
Current Neurovascular Research Scientific Prediction and Prophetic Patenting in Drug Discovery
Recent Patents on CNS Drug Discovery (Discontinued) PredCSF: An Integrated Feature-Based Approach for Predicting Conotoxin Superfamily
Protein & Peptide Letters Blood Pressure Reduction in the Primary and Secondary Prevention of Stroke
Current Vascular Pharmacology Predict Drug-Protein Interaction in Cellular Networking
Current Topics in Medicinal Chemistry Central Anti-Cholinergic Syndrome Induced by Single Therapeutic Dose of Atropine
Current Drug Safety Adeno-Associated Virus (AAV) Vectors in the CNS
Current Gene Therapy