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

Curr Drug Targets. 2019;20(11):1141-1155. doi: 10.2174/1389450120666190308144448.

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; chemokine (C-C motif) ligand 2; glucocorticoid receptor; immune inflammation; microglia..

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / chemistry
  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Blood-Brain Barrier
  • Cell Movement
  • Central Nervous System Diseases / metabolism*
  • Humans
  • RNA Stability
  • RNA, Messenger / chemistry
  • Receptors, Glucocorticoid / metabolism

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • RNA, Messenger
  • Receptors, Glucocorticoid