Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders.
Publication/Presentation Date
12-2-2015
Abstract
The strength of the blood-brain barrier (BBB) in providing protection to the central nervous system from exposure to circulating chemicals is maintained by tight junctions between endothelial cells and by a broad range of transporter proteins that regulate exchange between CNS and blood. The most important transporters that restrict the permeability of large number of toxins as well as therapeutic agents are the ABC transporters. Among them, P-gp, BCRP, MRP1 and MRP2 are the utmost studied. These efflux transporters are neuroprotective, limiting the brain entry of neurotoxins; however, they could also restrict the entry of many therapeutics and contribute to CNS pharmacoresistance. Characterization of several regulatory pathways that govern expression and activity of ABC efflux transporters in the endothelium of brain capillaries have led to an emerging consensus that these processes are complex and contain several cellular and molecular elements. Alterations in ABC efflux transporters expression and/or activity occur in several neurological diseases. Here, we review the signaling pathways that regulate expression and transport activity of P-gp, BCRP, MRP1 and MRP2 as well as how their expression/activity changes in neurological diseases. This article is part of a Special Issue entitled SI: Neuroprotection.
Volume
1628
Issue
Pt B
First Page
298
Last Page
316
ISSN
1872-6240
Published In/Presented At
Qosa, H., Miller, D. S., Pasinelli, P., & Trotti, D. (2015). Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders. Brain research, 1628(Pt B), 298–316. https://doi.org/10.1016/j.brainres.2015.07.005
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
26187753
Department(s)
Administration and Leadership
Document Type
Article