2023 Fiscal Year Final Research Report
New molecular mechanisms for membrane-mediated transcellular transport across the blood brain barrier
| Project/Area Number |
21H02649
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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) |
2021-04-01 – 2024-03-31
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| Keywords | 脳関門 / 脳毛細血管 / 膜輸送 / 内在化 / DDS / プロテオミクス |
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| Outline of Final Research Achievements |
Membrane-mediated transcellular transport of the blood-brain barrier (BBB) has attracted attention as a target for brain delivery. The aim of this study was to develop new knowledge on the transport mechanisms of the membrane-mediated transcellular transport of the BBB, the effects of target molecules on cell functions, and new analytical techniques based on the new findings of the principal investigators. The insulin receptor functions to maintain BBB function in brain capillaries. A newly identified internalized molecule, podocalyxin, is involved in the recycling of plasma membrane proteins. Furthermore, by integrating our original brain capillary isolation technology with the latest proteome analysis technology, we succeeded in obtaining high-depth BBB proteome information and clarified the diurnal variation of the BBB and changes in the BBB proteome in neonates. The results obtained will be important for understanding delivery and drug distribution to the brain in the future.
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| Free Research Field |
分子薬剤学
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| Academic Significance and Societal Importance of the Research Achievements |
脳へのdeliveryの標的分子はBBBに発現する内在性タンパク質であるため、分子本来の脳毛細血管に対する機能を有する。つまりdelivery標的としての機能と内在性機能が干渉する可能性があり、本研究の成果はそのような干渉を見積もるために重要な知見を与える。また、脳へのdelivery開発には種差が問題となっており、また、病態時に健常と同様に脳へ分布するかも重要である。本研究で開発した高深度BBBプロテオーム解析技術はそのような課題に重要な情報を与える技術である。
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