Blood-brain barrier active efflux transporters: ATP-binding cassette gene family |
| |
Authors: | Email author" target="_blank">Wolfgang?L?scherEmail author Heidrun?Potschka |
| |
Institution: | 1.Department of Pharmacology, Toxicology and Pharmacy,University of Veterinary Medicine Hannover, Foundation,Hannover,Germany |
| |
Abstract: | The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the brain from potentially harmful endogenous
and exogenous substances. BBB active drug efflux transporters of the ATP-binding cassette (ABC) gene family are increasingly
recognized as important determinants of drug distribution to, and elimination from, the CNS. The ABC efflux transporter P-glycoprotein
(Pgp) has been demonstrated as a key element of the BBB that can actively transport a huge variety of lipophilic drugs out
of the brain capillary endothelial cells that form the BBB. In addition to Pgp, other ABC efflux transporters such as members
of the multidrug resistance protein (MRP) family and breast cancer resistance protein (BCRP) seem to contribute to BBB function.
Consequences of ABC efflux transporters in the BBB include minimizing or avoiding neurotoxic adverse effects of drugs that
otherwise would penetrate into the brain. However, ABC efflux transporters may also limit the central distribution of drugs
that are beneficial to treat CNS diseases. Furthermore, neurological disorders such as epilepsy may be associated with overexpression
of ABC efflux transporters at the BBB, resulting in pharmacoresistance to therapeutic medication. Therefore, modulation of
ABC efflux transporters at the BBB forms a novel strategy to enhance the penetration of drugs into the brain and may yield
new therapeutic options for drug-resistant CNS diseases. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|