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Miller, David S
Trends in pharmacological sciences (Regular ed.), 06/2010, Letnik: 31, Številka: 6Journal Article
ATP-binding cassette (ABC) transporters are important selective elements of the blood–brain barrier. They line the luminal plasma membrane of the brain capillary endothelium, facing the vascular space, and both protect the central nervous system from entry of neurotoxicants and limit the access of therapeutic drugs to the brain parenchyma. Recent studies highlight the multiple signaling pathways through which the expression and activity of P-glycoprotein and other ABC transporters are modulated in response to xenobiotics, stress and disease. The results show that increased transporter expression occurs in response to signals that activate specific transcription factors, including pregnane-X receptor, constitutive androstane receptor, nuclear factor-κB and activator protein-1, and that reduced transporter activity occurs rapidly and reversibly in response to signaling through Src kinase, protein kinase C and estrogen receptors. A detailed understanding of such regulation can provide the basis for improved neuroprotection and enhanced therapeutic drug delivery to the brain.
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