Abstract
Since the discovery of P-glycoprotein (P-gp) in brain microvessels composing the human blood-brain barrier (BBB), ATPbinding cassette (ABC) transporters have been recognized as bottlenecks in the development and delivery of neuropharmaceuticals. ABC transporters are expressed predominately at the plasma luminal membrane of brain capillary endothelial cells. These ABC transporters are responsible for the efflux of their substrates from the endothelial cells to the bloodstream against the concentration gradient and thus limit the entry of some drugs within the central nervous system (CNS). Advanced quantitative molecular biology tools allowed gene and protein quantification of the components of microvessels isolated from different species including human. Recently, positron emission tomography using radiolabelled probes that are substrates of ABC transporters allowed the determination of their functional activity at the human BBB. Here, we summarized new information regarding the relative expression, substrate recognition pattern for CNS drugs and functional activity of ABC transporters that are quantitatively expressed at the human BBB.
Keywords: ATP-binding cassette transporters, blood-brain barrier, blood-cerebrospinal fluid barrier, P-glycoprotein, breast cancer resistance protein, multidrug resistance protein.
Current Pharmaceutical Design
Title:Human ABC Transporters at blood-CNS Interfaces as Determinants of CNS Drug Penetration
Volume: 20 Issue: 10
Author(s): Catarina Chaves, Ramzi Shawahna, Aude Jacob, Jean-Michel Scherrmann and Xavier Declèves*
Affiliation:
- Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris,France
Keywords: ATP-binding cassette transporters, blood-brain barrier, blood-cerebrospinal fluid barrier, P-glycoprotein, breast cancer resistance protein, multidrug resistance protein.
Abstract: Since the discovery of P-glycoprotein (P-gp) in brain microvessels composing the human blood-brain barrier (BBB), ATPbinding cassette (ABC) transporters have been recognized as bottlenecks in the development and delivery of neuropharmaceuticals. ABC transporters are expressed predominately at the plasma luminal membrane of brain capillary endothelial cells. These ABC transporters are responsible for the efflux of their substrates from the endothelial cells to the bloodstream against the concentration gradient and thus limit the entry of some drugs within the central nervous system (CNS). Advanced quantitative molecular biology tools allowed gene and protein quantification of the components of microvessels isolated from different species including human. Recently, positron emission tomography using radiolabelled probes that are substrates of ABC transporters allowed the determination of their functional activity at the human BBB. Here, we summarized new information regarding the relative expression, substrate recognition pattern for CNS drugs and functional activity of ABC transporters that are quantitatively expressed at the human BBB.
Export Options
About this article
Cite this article as:
Chaves Catarina, Shawahna Ramzi, Jacob Aude, Scherrmann Jean-Michel and Declèves Xavier*, Human ABC Transporters at blood-CNS Interfaces as Determinants of CNS Drug Penetration, Current Pharmaceutical Design 2014; 20 (10) . https://dx.doi.org/10.2174/13816128113199990466
DOI https://dx.doi.org/10.2174/13816128113199990466 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation
Current Pharmaceutical Design Recent Advances in Metabolomics
Current Metabolomics An Overview of Labeled Porphyrin Molecules in Medical Imaging
Recent Patents and Topics on Imaging (Discontinued) Addressing the Challenge: Current and Future Directions in Ovarian Cancer Therapy
Current Gene Therapy The Ubiquitous Choline Transporter SLC44A1
Central Nervous System Agents in Medicinal Chemistry EGFR-Targeting Monoclonal Antibodies in Head and Neck Cancer
Current Cancer Drug Targets Targeting IGF-I, IGFBPs and IGF-I Receptor System in Cancer: The Current and Future in Breast Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Extra-telomeric Functions of Human Telomerase: Cancer, Mitochondria and Oxidative Stress
Current Pharmaceutical Design Anti-Cancer Potential of Some Commonly Used Drugs
Current Pharmaceutical Design Immunostimulatory Oligonucleotides
Recent Patents on Inflammation & Allergy Drug Discovery Infringement of the Barriers of Cancer Via Dietary Phytoconstituents Capsaicin Through Novel Drug Delivery System
Current Drug Delivery Marine Natural Products and Related Compounds as Anticancer Agents: an Overview of their Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Group I Metabotropic Glutamate Receptor Signalling and its Implication in Neurological Disease
CNS & Neurological Disorders - Drug Targets C-11 Radiochemistry in Cancer Imaging Applications
Current Topics in Medicinal Chemistry Targeting the Multidrug ABCG2 Transporter with Flavonoidic Inhibitors: In Vitro Optimization and In Vivo Validation
Current Medicinal Chemistry The Synthesis and Use of Boronated Amino Acids for Boron Neutron Capture Therapy
Anti-Cancer Agents in Medicinal Chemistry Thalidomide: A Banned Drug Resurged into Future Anticancer Drug
Current Drug Therapy Destroying RNA as a Therapeutic Approach
Current Medicinal Chemistry Immune System Modulates the Function of Adult Neural Stem Cells
Current Immunology Reviews (Discontinued) Molecular Targeting Agents in Renal Cell Carcinoma: Present Strategies and Future Perspectives
Current Pharmaceutical Design