YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
受賞総説
生体関門輸送機能を基盤とした疾患メカニズムの解明と治療への展開
伊藤 慎悟
著者情報
ジャーナル フリー

2019 年 139 巻 4 号 p. 497-503

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Tissue barriers contribute to the maintenance of homeostasis in the body, and tissue barrier dysfunction presents a risk factor for a variety of diseases. The blood-brain barrier (BBB) is a major tissue barrier acting as a static barrier and dynamic interface that plays an important role in the maintenance of central nervous system homeostasis. We show the functional characterization of the brain-to-blood efflux transport system of amyloid-β peptide (Aβ) across the BBB. We found that activated vitamin D3 may be a candidate agent for modulating the Aβ clearance across the BBB. Cerebral creatine deficiency syndromes are caused by loss-of-function mutations in the creatine transporter (CRT; SLC6A8), which transports creatine at the BBB. We found that functional impairment of CRT due to a G561R mutation resulted in incomplete N-linked glycosylation due to misfolding during protein maturation, leading to impaired creatine transport activity at the BBB. To develop a delivery system for biomedicine across the tissue barrier, we established a screening system to identify cell-penetrating peptides by a combination of in vitro cell permeability screening assays and phage display technology. Using this system, we identified cyclic hepta-peptides that are able to facilitate intestinal absorption of phages in vitro and in vivo, which are promising candidates as a carrier for macromolecular biomedicines. In conclusion, these studies focusing on the dynamic interface of tissue barriers will contribute to knowledge on disease pathogenesis as well as the development of a targeted biomedicine delivery system.

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© 2019 The Pharmaceutical Society of Japan
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