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Published on: May 7, 2018
Transporters in the brain endothelial barrier
M Ueno1, T Nakagawa, B Wu
1Department of Pathology and Host Defense, Kagawa University, Miki-cho, Kita-gun, Japan. masaueno@med.kagawa-u.ac.jp
The blood-brain barrier (BBB) regulates substance transport. P-glycoprotein (P-gp) effluxes amyloid-beta and drugs, but its inhibition can aid drug delivery to the brain.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- The blood-brain barrier (BBB) controls substance exchange between blood and brain via various transport systems.
- P-glycoprotein (P-gp) is a key efflux transporter, removing amyloid-beta and drugs from the brain.
- BBB transporter dysfunction is implicated in neurodegenerative diseases.
Purpose of the Study:
- To review the role of BBB transporters in substance and drug movement.
- To discuss how P-gp and other transporters influence amyloid-beta clearance and drug brain penetration.
- To explore the therapeutic potential of modulating BBB transport.
Main Methods:
- Review of existing literature on BBB transport mechanisms.
- Analysis of the role of P-gp, LRP1, and RAGE in amyloid-beta and drug transport.
- Discussion of the implications of BBB transporter function in neurological disorders.
Main Results:
- P-gp deficiency increases amyloid-beta deposition in Alzheimer's models.
- Abeta deposition correlates inversely with P-gp expression in humans.
- Transient P-gp inhibition by antidepressants can enhance brain delivery of drugs like anti-cancer agents.
- LRP1 and RAGE are critical for Abeta efflux and influx across the BBB, respectively.
Conclusions:
- BBB transporters, including P-gp, LRP1, and RAGE, are crucial for maintaining brain homeostasis.
- Modulating BBB transport offers potential therapeutic strategies for neurodegenerative diseases and drug delivery.
- Understanding these transport systems is key to developing treatments for brain disorders.
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