Quantitative targeted proteomics for understanding the blood-brain barrier: towards pharmacoproteomics

Expert Rev Proteomics. 2014 Jun;11(3):303-13. doi: 10.1586/14789450.2014.893830. Epub 2014 Apr 4.

Abstract

The blood-brain barrier (BBB) is formed by brain capillary endothelial cells linked together via complex tight junctions, and serves to prevent entry of drugs into the brain. Multiple transporters are expressed at the BBB, where they control exchange of materials between the circulating blood and brain interstitial fluid, thereby supporting and protecting the CNS. An understanding of the BBB is necessary for efficient development of CNS-acting drugs and to identify potential drug targets for treatment of CNS diseases. Quantitative targeted proteomics can provide detailed information on protein expression levels at the BBB. The present review highlights the latest applications of quantitative targeted proteomics in BBB research, specifically to evaluate species and in vivo-in vitro differences, and to reconstruct in vivo transport activity. Such a BBB quantitative proteomics approach can be considered as pharmacoproteomics.

Keywords: absolute quantification; blood–brain barrier; brain capillary endothelial cells; multiple reaction monitoring; pharmacoproteomics; quantitative targeted proteomics; transporter.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Biological Transport
  • Blood-Brain Barrier / metabolism*
  • Brain / blood supply
  • Endothelial Cells / metabolism
  • Humans
  • Proteome / metabolism*
  • Species Specificity

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Proteome