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

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, P-gp 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.