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

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

Journal Name: Current Drug Targets

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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

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(E-pub Ahead of Print)
DOI: 10.2174/1389450120666190308144448
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