Quantitative targeted proteomics for understanding the blood-brain barrier: towards pharmacoproteomics.
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.
Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Sumio
S
Ohtsuki
Mio
M
Hirayama
Shingo
S
Ito
Yasuo
Y
Uchida
Masanori
M
Tachikawa
Tetsuya
T
Terasaki
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D020543:Proteome / Q000378:metabolism*; D013045:Species Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020543:Proteome
absolute quantification; blood–brain barrier; brain capillary endothelial cells; multiple reaction monitoring; pharmacoproteomics; quantitative targeted proteomics; transporter