Mcrotransport of the blood-brain barrier and its application to the permeable carrier.
| Project/Area Number |
18H02590
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
OHTSUKI Sumio 熊本大学, 大学院生命科学研究部(薬), 教授 (60323036)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 慎悟 熊本大学, 大学院生命科学研究部(薬), 准教授 (20466535)
増田 豪 熊本大学, 大学院生命科学研究部(薬), 助教 (70383940)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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| Keywords | 血液脳関門 / 脳毛細血管 / 膜タンパク質 / 輸送 / プロテオミクス / 内在化 / DDS / 脳関門 |
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| Outline of Final Research Achievements |
This study aimed to elucidate the molecular mechanisms of medium and macromolecular transport systems at the blood-brain barrier and develop DDS carriers that can facilitate penetration across the blood-brain barrier. We have established methods for comprehensive analysis of internalized proteins and for isolating brain capillaries with high purity. We conducted a comparative analysis of the internalization proteome between human brain capillary endothelial cells and human umbilical vein endothelial cells, and identified blood-brain barrier-selective internalization molecules. We also identified a blood-brain barrier-permeable cyclic peptide, indicating the involvement of a new permeation mechanism. In addition, we found that the modification of the identified cyclic peptides facilitates the brain distribution of liposomes
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では脳への高分子移行に関わると考えられる脳毛細血管内皮細胞に発現する内在化分子を同定した。また、環状ペプチドの血液脳関門透過性機構としてエクソソーム分泌系の関与を明らかにした。これらの成果は血液脳関門の新たな生理機能の解明につながる事が期待される。また、同定した環状ペプチドは巨大粒子であるファージの脳移行を促進させることが従来のDDSキャリアに対する優位点である。従って、同定環状ペプチドを活用することによってナノ粒子による効率的な脳への薬物送達が可能になり、新たな中枢疾患治療薬開発に貢献することが期待される。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Large-Scale Quantitative Comparison of Plasma Transmembrane Proteins between Two Human Blood-Brain Barrier Model Cell Lines, hCMEC/D3 and HBMEC/cibeta.2019
Author(s)
Masuda T, Hoshiyama T, Uemura T, Hirayama-Kurogi M, Ogata S, Furukawa A, Couraud PO, Furihata T, Ito S, Ohtsuki S
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Journal Title
Mol Pharm
Volume: 16
Issue: 5
Pages: 2162-2171
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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