Pathogenesis of Alzheimer's disease based on vesicular transport system in neuron
| Project/Area Number |
18H02566
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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 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
羽田 沙緒里 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (40581012)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | アルツハイマー病 / 認知症 / アミロイドβ / 軸索輸送 / キネシン－1 / キネシン / 微小管 / 膜小胞輸送 / 孤発性*アルツハイマー病 / 神経細胞 / APP / 神経軸索 / 神経 |
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| Outline of Final Research Achievements |
Our aim is to reveal a molecular mechanism of sporadic Alzheimer’s disease (AD). We focused our analysis on the relationship APP function and metabolism. In neurons, APP serves a cargo receptor of molecular motor. When APP connects with motor molecule by mediation of adaptor protein JIP1, the membrane vesicle of APP is transported with high efficiency, which tends to suppress the neurotoxic amiloid-beta (Ab) generation from APP (our previous reports). In this study, we found that APP can directly associate with molecular motor when adaptor protein is defective. In such case, transport efficiency of APP vesicles reduced, which can induce increased generation of Ab. In aged brain, we explore whether altered transport of APP vesicles occurs along with increased Abeta generation.
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| Academic Significance and Societal Importance of the Research Achievements |
我が国では500万人以上の認知症患者が存在し、その70%はアルツハイマー病であるが、根本治療薬は無く予防と対処療法が中心となっている。高齢者の増加に伴い根本治療薬の開発は社会的な要請である。根本治療薬開発を妨げている要因は、孤発性のADの発症機構が多様で、発症メカニズムがよく理解されていない点である。研究代表者は、発症原因因子アミロイドβの前駆体APPの機能が、神経細胞内の軸索輸送を担うカーゴ受容体分子であることを世界に先駆けて示してきた。このAPPの機能とAβを生み出す代謝との関係を解明する研究は、根本治療薬の開発に必要となる新たな創薬標的を生み出す意義を持つ。
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Extracellular release of ILEI/FAM3C and amyloid-β is associated with the activation of distinct synapse subpopulations.2021
Author(s)
Nakano M, Mitsuishi Y, Liu L, Watanabe N, Hibino E, Hata S, Saito T, Saido C T, Murayama S, Kasuga K, Ikeuchi K, Suzuki T, Nishimura M
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Journal Title
Journal of Alzheimer’s disease
Volume: 80
Issue: 1
Pages: 159-174
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Generation of transgenic cynomolgus monkeys overexpressing the gene for amyloid-β precursor protein2020
Author(s)
Seita Y, Morimura T, Watanabe N, Iwatani C, Tsuchiya H, Nakamura S, Suzuki T, Yanagisawa D, Tsukiyama T, Nakaya M, Okamura E, Muto M, Ema M, Nishimura M, Tooyama I.
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Journal Title
Journal of Alzheimer's Disease
Volume: -
Issue: 1
Pages: 45-60
DOI
NAID
Related Report
Peer Reviewed / Open Access
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