| Project/Area Number |
18K19380
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 46:Neuroscience and related fields
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| Research Institution | Keio University |
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Principal Investigator |
SUZUKI Kunimichi 慶應義塾大学, 医学部(信濃町), 特任助教 (10713703)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | シナプス / C1q / 脊髄損傷 / AMPA受容体 / Cbln / シナプスオーガナイザー / ナノボディ |
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| Outline of Final Research Achievements |
This research aims to develop novel artificial synapse organizers, which connect synapses of interest, to cure the diseases caused by the loss of the synaptic connections. Investigation of NPTX family proteins, complement C1q and nanobodies against glutamate receptors revealed the physiological function, novel receptors and binding profiles, making the progress in the further design of the new artificial synapse organizers. Detailed analysis of the excitatory artificial synapse organizers which had been already designed revealed the basic mechanism for the brain circuits and molecules. As an application to the diseases, it turned out that the motor deficit caused by spinal cord injury was improved by the excitatory artificial organizer, demonstrating the promising evidence as the novel therapeutic tool for synapse diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、脳内に存在するシナプス接着分子の構造を原案として改変し、様々なシナプス形成・維持・除去を可能とする人工的シナプスオーガナイザー開発しようとする挑戦的な研究であったが、この概念を試験管レベルから動物レベルまで証明すると同時に、新たな人工的分子の合理的な設計のための所見が蓄積され、分子機構や神経回路を解明する基礎的な知見が得られた。さらにシナプスの減少により引き起こされる疾患が治療可能であることが見いだされ、新規の疾患治療法開発に繋がる新規概念を確立し、現実的な医療への応用につながる研究となった。
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