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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.
Acknowledgements
The studies mentioned in this review were supported in part by a Grant for Development of Creative Technology Seeds Supporting Program for Creating University Ventures and a grant for Creation of Strategic Innovation Project from the Japan Science and Technology Agency (JST), and the Industrial Technology Research Grant Program from New Energy and the Industrial Technology Development Organization (NEDO) of Japan, as well as the funding program for Next Generation World-Leading Researchers by the Cabinet Office, Government of Japan.
Financial & competing interests disclosure
S Ohtsuki and T Terasaki are full professors of Kumamoto University and are also directors of Proteomedix Frontiers. This work was not supported by Proteomedix Frontier and their positions there do not present any financial conflicts. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
The blood–brain barrier (BBB) prevents entry of drugs into the brain, and understanding BBB permeability mechanisms and transport systems are necessary for developing CNS-acting drugs.
To understand the human BBB, it is necessary to identify expressed molecules, to clarify species differences and in vivo–in vitro differences, and to estimate transport function in humans. Highly sensitive, accurate and specific protein quantification by quantitative targeted proteomics are essential methodology for human BBB studies.
Comparison of protein expression levels by quantitative targeted proteomics is an effective strategy for validating animal and in vitro models.
Accurate protein quantification by quantitative proteomics enables us to reconstruct in vivo transport function at the BBB using protein expression information in vivo and in vitro and intrinsic transport activity obtained in vitro.
The importance of quantitative proteomic analysis in BBB research is increasing and will lead to a better understanding of patients’ BBB function, as well as improving methodology for drug delivery to the brain.