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

[ Vol. 20 , Issue. 11 ]

Author(s):

Liangliang Huang, Binbin Li, Xiang Li, Ge Liu, Rui Liu, Jia Guo, Baohui Xu, Yunman Li* and Weirong Fang*   Pages 1141 - 1155 ( 15 )

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.

Affiliation:

State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009

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