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Induction of P-glycoprotein overexpression in brain endothelial cells as a model to study blood-brain barrier efflux transport

Sarah F. Hathcock, Hallie E. Knight, Emma G. Tong, Alexandra E. Meyer, Henry D. Mauser,Nadine Vollmuth,Brandon J. Kim,Brandon J. Kim,Brandon J. Kim,Brandon J. Kim

Frontiers in Drug Delivery(2024)

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摘要
The blood-brain barrier (BBB) is comprised of specialized brain endothelial cells (BECs) that contribute to maintaining central nervous system (CNS) homeostasis. BECs possess properties such as an array of multi-drug efflux transporters that eject various drugs and toxins, preventing their entry into the CNS. Together, it is estimated that these efflux transporters can eject up to 98% of known xenobiotic compounds. P-glycoprotein (P-gp) is a promiscuous efflux transporter at the BBB and can efflux up to 90 various substrates, representing a major hurdle in CNS drug delivery for therapeutic interventions. This necessitates the study of P-gp to discover drugs that are non-substrates of P-gp as well as to identify novel P-gp inhibitors. Here we report the generation of P-gp overexpressing BECs under the endogenous promoter control that could be used in the screening of P-gp substrates. These cells could provide utility in the design of drugs or identification of novel inhibitors.
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关键词
blood-brain barrier,P-glycoprotein,efflux transport,drug screening,brain endothelial cells,puromycin
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