Multi-disciplinary research approaches on the brain barrier transport system, a dynamic interface

Masanori Tachikawa, Yasuo Uchida, Tetsuya Terasaki

研究成果: Review article

3 引用 (Scopus)

抜粋

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) possess a variety of carrier-mediated transport systems to support and protect brain function. Multidisciplinary research conducted on these transport systems has provided a foundation not only for understanding the pathophysiological role of the brain barriers better but also for the development of rational drug delivery and targeting strategies for the central nervous system (CNS). Drugs recognized by the blood-to-brain influx transport systems, e.g., an amino acid transporter LAT1/SLC7A5 and an unidentified organic cation transporter, are expected to have a great potential for CNS delivery. Nevertheless, drugs recognized by efflux transporters, including ATP-binding cassette transporters such as P-glycoprotein (MDR1/ABCB1), breast cancer resistance protein (BCRP/ABCG2) and multidrug-resistant protein 4 (MRP4/ABCC4), show low permeability across the brain barriers, resulting in low distribution to the brain. The brain-to-blood efflux transport systems also play an important role in the cerebral clearance of endogenous neurotoxic compounds such as prostaglandins and β-amyloid, the reduction of which is related to disorders of the CNS. Recently, we developed a method based on quantitative targeted absolute proteomics (QTAP) to determine the absolute expression levels of transporters of the human brain barriers. Data on absolute expression levels of transporters together with data on intrinsic transporter activity enables reconstruction of in vivo brain barrier transport function in humans. This review covers cutting-edge knowledge and methodologies related to transport systems at the BBB and BCSFB, which contribute to the knowledge regarding the management of endogenous and xenobiotic compounds by the brain, and the importance of these transport systems for CNS drug delivery and therapeutics.

元の言語English
ページ(範囲)121-136
ページ数16
ジャーナルBrain and Nerve
65
発行部数2
出版物ステータスPublished - 2013 2 1

ASJC Scopus subject areas

  • Clinical Neurology

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