| Project/Area Number |
18H02585
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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 | Kindai University (2019-2021)
Osaka University (2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
皆川 栄子 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 モデル動物開発研究部, 客員研究員 (20726252)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | 神経変性疾患 / エクソソーム / プロテオスターシス / バイオマーカー / 環境因子 / 環境要因 |
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| Outline of Final Research Achievements |
Protein misfolding and aggregation are associated with the onset and progression of many neurodegenerative diseases. Previously we reported that secretion and transmission of molecular chaperones via exosomes, one of the extracellular vesicles (EVs), suppress neurodegeneration in a non-cell autonomous manner, contributing to maintenance of organismal protein homeostasis. To elucidate the molecular mechanisms, here we performed comprehensive analysis of EV contents using the cellular and animal models of the polyglutamine diseases, one of the neurodegenerative diseases. We found that a cellular factor is responsible for secretion of molecular chaperones via EVs. We also found that several EV proteins are altered in the disease models, some of which are confirmed in patients. Our data provide not only insight into the mechanism of EV-mediated secretion of chaperones but also a promising platform for the development of EV-based biomarkers for the neurodegenerative diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、エクソソームを介した細胞非自律的プロテオスターシス維持機構の分子機序の一端が明らかとなった。また、神経変性疾患におけるエクソソーム分泌の変容が明らかとなり、病態機序との関連が示唆された。さらに、ポリグルタミン病における血液エクソソームタンパク質の変容が網羅的に明らかとなり、神経変性疾患の病態診断バイオマーカー候補分子が同定された。
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