Study of alpha-synuclein propagation by in vivo structural analysis at SPring-8
| Project/Area Number |
16K09716
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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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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
Katsuya Araki 大阪大学, 医学系研究科, 特任研究員 (50649431)
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| Co-Investigator(Kenkyū-buntansha) |
藪本 大紀 大阪大学, 医学部附属病院, 医員 (20774227)
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| Research Collaborator |
MOCHIZUKI Hideki
YAGI Naoto
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | パーキンソン病 / α-シヌクレイン / レビー小体 / アミロイドーシス / アミロイド線維 / SPring-8 / 放射光 / 量子ビーム / 神経内科学 / 多系統萎縮症 / アミロイド繊維 / プリオン / 構造解析 / 伝播 / 神経変性疾患 |
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| Outline of Final Research Achievements |
Lewy body and glial cytoplasmic inclusion (GCI) are characteristic aggregates found in the brain of patients with Parkinson's disease and multiple system atrophy, respectively, and are mainly consist of α-synuclein. Recently, it has been reported that these aggregates are capable of propagating within the brain in a prion-like manner. However, in these study, artificial amyloid fibrils of α-synuclein are used and there is still no evidence that such propagation occurs in the patient's brain. Here, we challenged for ultrastructural analysis of aggregates in the autopsy brain using SPring-8 synchrotron radiation, which has been considered difficult until now.
As a result, it was found for the first time that Lewy body contains amyloid fibrils, and the secondary structural difference between Lewy body and GCI also was clarified.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究成果は，これまで行われてきた人工的なアミロイド線維を用いた実験の正当性を支持するものであり，すでに進められている臨床研究を後押しする重要な成果である．また，本研究成果はパーキンソン病がアミロイドーシスの一種であるという新しい概念を提唱するものであり，革新的治療開発の手がかりとなり得るものである．
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.2019
Author(s)
2. Kakuda K, Ikenaka K, Araki K, So M, Aguirre C, Kajiyama Y, Konaka K, Noi K, Baba K, Tsuda H, Nagano S, Ohmichi T, Nagai Y, Tokuda T, El-Agnaf O, Ogi H, Goto Y, Mochizuki H.
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Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 6001-6001
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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