Basic and applied research on the secreted protein, Reelin, oriented toward the understanding and treatment of psychiatric disorders.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03384
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Nagoya City University
• Principal Investigator: Hattori Mitsuharu 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (60272481)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: リーリン / プロテアーゼ / 神経細胞 / 精神神経疾患 / 脂質 / リン酸化 / 遺伝子改変マウス

Outline of Final Research Achievements

Research was conducted to gain a comprehensive understanding of the function of Reelin and its molecular mechanisms in the expression of higher-order functions in the adult brain, and to develop novel therapies for psychiatric disorders. We found that the C-terminal region of Reelin enhances signaling through a novel receptor, that the Reelin-degrading enzyme ADAMTS-3 regulates oligodendrocyte migration, that ADAMTS-3 inhibition in the postnatal brain ameliorates Alzheimer's disease, and that administration of Reelin to the postnatal cerebellum partially restores behavioral abnormalities.

Free Research Field

分子神経科学

Academic Significance and Societal Importance of the Research Achievements

神経回路網の正確な形成と成体神経回路の機能調節機構の解明は、精神神経疾患の理解と治療法開発のために重要である。本研究では、これらの現象に重要な分泌タンパク質の機能解明と、その治療への応用についての基礎研究を実施した。その成果から、新たな創薬標的、および、先天性脳形成不全に対する治療法の突破口が得られた。