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- Structure of the blood-brain barrier
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1. The blood-brain barrier in Alzheimer’s disease
- Dr. Anika Hartz
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2. Tanycytes allow a tight BBB in the median eminence
- Prof. Esteban Rodriguez
- Dr. Juan Luis Blazquez
- Dr. Montserrat Guerra
- Nutrient transport
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3. Blood-brain barrier ion transport
- Prof. Martha O'Donnell
- Peptides and proteins
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4. Ingestive peptides
- Prof. William Banks
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5. Blood-brain barrier in health and disease
- Prof. Thomas Davis
- Overcoming the blood-brain barrier obstacle
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6. Expression vs. function of ABC transporters at the blood-brain barrier
- Prof. Jean-Michel Scherrmann
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7. The blood-brain barrier and CNS drug development
- Dr. Danica Stanimirovic
- Diseases involving the blood-brain barrier
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9. Inflammation and immune cell entry to the central nervous system
- Prof. Serge Rivest
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11. Ischemic blood-brain barrier and Alzheimer's amyloid plaques development
- Prof. Ryszard Pluta
- Latest Developments in the Field
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12. MRI approaches for neurovascular imaging
- Dr. Rick Dijkhuizen
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13. Brain-gut interactions in obesity 1
- Prof. Weihong Pan
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14. Brain-gut interactions in obesity 2
- Prof. Weihong Pan
- Archived Lectures *These may not cover the latest advances in the field
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15. Neurotrophins and the BBB
- Prof. Weihong Pan
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16. Vasoactive peptides and the blood-brain barrier
- Prof. Maria Deli
- Prof. Bela Kis
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17. In vivo systems
- Prof. Quentin Smith
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18. CNS-drug design
- Prof. Quentin Smith
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20. Stroke and the BBB
- Prof. Marilyn Cipolla
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21. Barrier mechanisms in the developing brain: mechanisms and misunderstandings
- Prof. Norman Saunders
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22. Barrier mechanisms in the developing brain: protection or vulnerability?
- Prof. Norman Saunders
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23. In vitro models of the blood-brain barrier
- Prof. Pierre-Olivier Couraud
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24. Glucose transport across the blood-brain barrier
- Prof. Luc Leybaert
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25. The blood-brain barrier and brain tumors
- Dr. Olaf van Tellingen
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26. Cellular composition of the blood-brain barrier
- Prof. N. Joan Abbott
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27. Features of mammalian CNS barrier systems
- Prof. Conrad Johanson
Printable Handouts
Navigable Slide Index
- Introduction
- Outline (1)
- The ABC Superfamily
- P-Glycoprotein: pioneer and leader
- Structural biology and molecular activity: P-gp
- ABC transporters in the neuro-glio vascular unit
- Role of the ABC proteins at the BMECs?
- Outline (2)
- ABCB and P-gp (ABCB1) at the BBB
- P-glycoprotein: the gatekeeper at the BBB
- P-gp expression in the cerebral vasculature
- Imaging the function of P-gp
- P-glycoprotein at the BBB: quantitative impact
- What have we not learnt from these experiments?
- Brain distribution volume & uptake parameters
- Linear brain uptake flux for morphine & colchicine
- Non-linear brain uptake of a taxoid derivative
- Non-linear brain level of TXD 258
- Brain uptake clearance (Kin) for TXD258 in rodents
- P-gp mediated drug-drug interaction at BBB (1)
- P-gp mediated drug-drug interaction at BBB (2)
- PET imaging P-gp transport activity in humans
- Outline (3)
- ABCG and ABCG2 (BCRP) at the BBB
- Co-immunolocalization of P-gp & BCRP
- BCRP protects against photoxins & protoporphyria
- BBB transport of mitoxantrone by ABCG2
- Expression of ABCG2 in brain cortex & capillaries
- P-gp & BCRP in tandem at BBB: imatinib
- Kinetics of imatinib brain transport at BBB (1)
- Kinetics of imatinib brain transport at BBB (2)
- Influence of Mdr1a & BCRP1 (1)
- Influence of Mdr1a & BCRP1 (2)
- Transport of CGP74588 to the brain
- P-gp & BCRP: two gatekeepers in the BBB
- P-gp & BCRP limit the penetration of topotecan
- Outline (4)
- Where and which MRPs (ABCCs) at the BBB?
- Localization of ABCC transporters in the brain (1)
- Localization of ABCC transporters in the brain (2)
- ABCC transporters at the neuro-glio vascular unit
- Mrp1-mediated efflux at the luminal side
- Lack of Nrp-1-mediated efflux at the luminal side
- Mrp4-mediated efflux at the BBB and BCSFB
- Outline (5)
- Quantitative expression of ABC at the human BBB
- Purity of human brain cortical microvessels
- Relative gene expression of ABC transporters
- Protein amounts in human brain microvessels
- Expression of ABC in human brain microvessels
- Comparing brain microvessels and cortex
- Outline (6)
- Extrapolation (1)
- Questions on interspecies scaling
- ABC differences between in vivo/in vitro BBB
- Efflux ratio = BA/AB
- P-gp efflux ratio for opioids
- Buprenorphine case
- Extrapolation (2)
- Interspecies differences in expression
- Conclusions (1)
- Conclusions (2)
- Conclusions (3)
- The contributors
- Still on the ABC road to better know BBB
Topics Covered
- Introduction to the ABC superfamily and the blood-brain barrier (BBB)
- ABCB and P-glycoprotein (ABCB1) at the BBB
- ABCG and BCRP (ABCG2) at the BBB
- ABCC and the Multi-Drug Resistance Proteins (MRPs) at the BBB
- ABC in isolated human brain microvessels
- Pre-clinical and clinical impact in central nervous system research and drug development
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Scherrmann, J. (2019, February 3). Expression vs. function of ABC transporters at the blood-brain barrier [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 4, 2024, from https://doi.org/10.69645/QNTG2691.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Jean-Michel Scherrmann has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neurology
Transcript
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0:00
"Expression versus Function of ABC Transporters at the Blood-Brain Barrier".
I am Jean-Michel Scherrmann,
I am professor of Pharmacokinetics at
the Faculty of Pharmacie of Paris Descartes University.
0:14
During my presentation, I will give
some general properties on the ABC transporters and on the blood-brain barrier.
I will describe P-glycoprotein or ABCB1, BCRP,
or ABCG2, and the multi-drug resistant proteins,
the MRPs at the level of the blood-brain barrier.
In the last part, I will report our data on the gene and
protein expression of this ABC in the human brain microvessels.
And finally, I will conclude my presentation by
the impact that these ABC transporters in the blood-brain barrier can have,
in the research and development of central nervous system drugs.
1:01
The ABC transporters belong to a superfamily with 48 reported genes in humans.
Four subfamilies, A, B, C,
and G contain several isoforms,
which are implied in drug transport.
The most known is a full transporters ABCB1 or P-glycoprotein,
which is mostly expressed in the plasma membrane,
but also in some sub-cellular sites,
like other ABC proteins.
This raises the question of
the ABC transporter role in the intracellular drug disposition.
Nevertheless, the subfamily D, E,
and F do not seem involved in
the transport and expressed at the level of the blood-brain barrier.
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