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Current Drug Targets

Author(s): Liangliang Huang, Binbin Li, Xiang Li, Ge Liu, Rui Liu, Jia Guo, Baohui Xu, Yunman Li* and Weirong Fang*

DOI: 10.2174/1389450120666190308144448

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Significance and Mechanisms of P-glycoprotein in Central Nervous System Diseases

Page: [1141 - 1155] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

P-glycoprotein (P-gp) is a member of ATP-Binding Cassette (ABC) transporter family. Because of its characteristic luminal surface location, high transport potency and structural specificity, Pgp is regarded as a selective gatekeeper of the Blood Brain Barrier (BBB) to prevent the entry of toxins or unwanted substances into the brain. In recent years, increasing evidence has shown that P-gp is involved in the immune inflammatory response in the Central Nervous System (CNS) disorders by regulating microglia activation, and mediating immune cell migration. Furthermore, Glucocorticoid Receptor (GR) may play a crucial role in P-gp-mediated microglia activation and immune cell migration via GR-mediated mRNA decay. In this article, we will review P-gp structure, distribution, function, regulatory mechanisms, inhibitors and effects of P-gp in the pathogenesis of several CNS diseases and will discuss the role of P-gp in microglia activation, immune cell migration and the relationship with cytokine secretion.

Keywords: P-glycoprotein, central nervous system, immune inflammation, glucocorticoid receptor, microglia, chemokine (C-C motif) ligand 2.

Graphical Abstract

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