2021 Fiscal Year Final Research Report
Analysis of human-specific regulation of neural function by V-1/CP complex and its therapeutic application for aging-related disorders
| Project/Area Number |
19K07097
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | パーキンソン病 / ドパミン / V-1/CP複合体 / 脂肪酸結合タンパク質 / αシヌクレイン / ドパミン受容体 / カベオラ依存的エンドサイトーシス / レビー小体病 |
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| Outline of Final Research Achievements |
With the aging of the population, the number of Parkinson's patients has reached one million, and there is currently no fundamental therapeutics for the disease. We have identified a novel actin polymerization regulator V-1/CP complex and its physiological function that potently activates midbrain dopaminergic neurons that are lost in Parkinson's disease. However, the molecular mechanism of why the complex disappears during aging and neurodegeneration was not clear. In this study, we found that the complex disappears in Parkinson's disease and that the fatty acid-binding protein FABP3 is an intrinsic upstream factor of the complex. We also demonstrated the mechanism of propagation and aggregation of the protein responsible for Parkinson's disease by FABP3 and the therapeutic effect of FABP3 inhibitors, making it possible to apply the therapeutics to aging-related disorders.
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| Free Research Field |
神経薬理学、応用薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題では、超高齢化社会の到来により増加するパーキンソン病の新たな発症機序を理解することで、独自の根本的予防法を確立する学術的意義がある。ドパミン機能の維持に必須である新規V-1/CP複合体が、なぜ加齢や神経疾患において消失するのかを明らかにすることで、V-1/CP複合体とその内在性上流因子を標的とした新たなドパミン疾患の予防・治療法を確立し、高齢化社会における健康長寿社会に貢献可能である社会的意義がある。加齢や疾患における同複合体の消失を予防可能な内在性分子とその標的化合物を見出すことで、細胞移植に頼らない新たなパーキンソン病の根本的な予防・治療法の確立が期待できる。
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