Transmission mechanism of abnormal conformational transition of polyglutamine protein
Project/Area Number |
17K09755
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Osaka University |
Principal Investigator |
Ozawa Daisaku 大阪大学, 医学系研究科, 特任助教 (60554524)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | ポリグルタミン / アミロイド / 神経変性疾患 / プリオン / ポリグルタミン蛋白質 |
Outline of Final Research Achievements |
Abnormal conformational change of proteins is thought to be a common molecular mechanism of many neurodegenerative diseases. In prion hypothesis, it has been proposed that monomeric misfolded proteins transmit its abnormal structure to native proteins and then form newly misfolded protein monomers. However, the prion hypothesis has not been experimentally proven yet. Moreover, whether the similar phenomenon occurs in other disease-related proteins is unknown. Here, we examined the molecular mechanism of conformational transmission of polyglutamine protein. We revealed that monomeric β-sheet thio-polyQ transmits its β-sheet structure to monomeric α-helix thio-polyQ and then replicates newly monomeric β-sheet thio-polyQ. These results revealed the prion-like conformational transmission between polyglutamine protein monomers, providing experimental evidence for the prion hypothesis. It may be a common phenomenon for neurodegenerative diseases-related proteins.
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Academic Significance and Societal Importance of the Research Achievements |
本研究による蛋白質のミスフォールディングの実態と異常コンフォメーションの伝播機構の解明は、神経変性疾患で起きうる蛋白質のプリオン現象の共通の分子機構の理解に貢献する。さらに、神経変性疾患の治療・予防法の開発への応用が期待できる。
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Report
(5 results)
Research Products
(11 results)
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[Journal Article] Arginine is a disease modifier for polyQ disease models that stabilizes polyQ protein conformation.2020
Author(s)
Minakawa EN, Popiel HA, Tada M, Takahashi T, Yamane H, Saitoh Y, Takahashi Y, Ozawa D, Takeda A, Takeuchi T, Okamoto Y, Yamamoto K, Suzuki M, Fujita H, Ito C, Yagihara H, Saito Y, Watase K, Adachi H, Katsuno M, Mochizuki H, Shiraki K, Sobue G, Toda T, Wada K, Onodera O, Nagai Y.
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Journal Title
Brain
Volume: 143
Issue: 6
Pages: 1811-1825
DOI
Related Report
Peer Reviewed
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[Book] 相分離生物学の全貌2020
Author(s)
小澤大作、永井義隆
Total Pages
416
Publisher
東京化学同人
ISBN
9784807913466
Related Report
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