title: Frizzled fissure to improve central nervous system drug delivery?
abstract: Delivery of therapeutics to the brain is challenging because of efflux pumps located in the vascular endothelium. A detailed analysis of Wnt signaling in a human brain endothelial cell line indicates that expression and function of P-glycoprotein, a major efflux transporter, is controlled by non-canonical Wnt signaling. Inhibition of this pathway leads to downregulation of P-glycoprotein and increased transcellular drug transport and reveals a potential strategy for improving drug delivery for treatment of neurologic diseases.
authors.affiliation: Department of Biomedical Sciences and Brain Barriers Research Center, University of Minnesota Medical School Duluth, Duluth, Minnesota, USA.
authors.forename: Lester R
authors.initials: LR
authors.lastname: Drewes
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051176:beta Catenin; C066737:RHOA protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D054460:rho-Associated Kinases; D038362:Glycogen Synthase Kinase 3; D020742:rhoA GTP-Binding Protein