title: Role of nuclear receptors in the regulation of drug transporters in the brain.
abstract: ATP-binding cassette membrane-associated drug efflux transporters and solute carrier influx transporters, expressed at the blood-brain barrier, blood-cerebrospinal fluid barrier, and in brain parenchyma, are important determinants of drug disposition in the central nervous system. Targeting the regulatory pathways that govern the expression of these transporters could provide novel approaches to selectively alter drug permeability into the brain. Nuclear receptors are ligand-activated transcription factors which regulate the gene expression of several metabolic enzymes and drug efflux/influx transporters. Although efforts have primarily been focused on investigating these regulatory pathways in peripheral organs (i.e., liver and intestine), recent findings demonstrate their significance in the brain. This review addresses the role of nuclear receptors in the regulation of drug transporter functional expression in the brain. An in-depth understanding of these pathways could guide the development of novel pharmacotherapy with either enhanced efficacy in the central nervous system or minimal associated neurotoxicity.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 3M2, Canada.
authors.forename: Gary N Y
authors.initials: GN
authors.lastname: Chan
authors.forename: Md Tozammel
authors.initials: MT
authors.lastname: Hoque
authors.forename: Reina
authors.initials: R
authors.lastname: Bendayan
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016623:Ion Pumps / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D016623:Ion Pumps; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D018160:Receptors, Cytoplasmic and Nuclear