Pathogenesis and treatment of multiple system atrophy
| Project/Area Number |
16K09672
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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 | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 多系統萎縮症 / 脳神経疾患 |
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| Outline of Final Research Achievements |
Multiple system atrophy (MSA) is characterized by the accumulation of aggregated alpha-synuclein (aS), but the mechanism underlying specific accumulation of pathological aS in oligodendrocyte is largely unknown and effective therapies have not been established yet. Recent studies suggested that brain lysates from MSA brains induced aS propagation in neurons, but not in oligodendrocytes, and thus mechanism of specific accumulation of aS in oligodendrocyte still remained unknown. In this study we showed that aS aggregates existed in exosomes which were derived from MSA brains, and exosomes derived from MSA brains were capable of inducing the oligodendrocytic inclusion of aS in mice. From these data cell-type specific exoxomes are possibly involved in cell-specific transfer of disease-associated pathological proteins, and can be a target of the disease-modifying therapy in a-synucleinopathy.
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| Academic Significance and Societal Importance of the Research Achievements |
多系統萎縮症（MSA）はαシヌクレイン（αsyn）の蓄積を主徴とするが、オリゴデンドロサイト（ODC）特異的なαsyn蓄積の原因は全く不明であり、現在有効な治療法もない。最近、MSA脳抽出液の接種により、蓄積したαsynは神経細胞に伝播することが証明されたが、ODC特異的な伝播メカニズムは不明であった。本研究において、MSA脳から抽出したエクソソーム内に凝集αsynが存在し、マウスODCに伝播しうることが示唆された。これにより、MSAにおけるODC特異的なαsyn伝播の一部はエクソソームが関与することが示され、これを標的としたαシヌクレイノパチーの治療法の可能性が示された。
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Report
(5 results)
Research Products
(28 results)
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[Journal Article] a-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia:a prodromal Parkinson’s disease model2020
Author(s)
Taguchi T, Ikuno M, Hondo M, Parajuli LK, Taguchi K, Ueda J, Sawamura M, Okuda S, Nakanishi E, Hara J, Uemura N, Hatanaka Y, Ayaki T, Matsuzawa S, Tanaka M, El-Agnaf OMA, Koike M, Yanagisawa M, Uemura MT, Yamakado H, Takahashi R
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Journal Title
BRAIN
Volume: 143
Issue: 1
Pages: 249-265
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Diagnostic utility of FDG-PET in neurolymphomatosis: report of five cases.2016
Author(s)
Kinoshita H, Yamakado H, Kitano T, Kitamura A, Yamashita H, Miyamoto M, Hitomi T, Okada T, Nakamoto Y, Sawamoto N, Takaori-Kondo A, Takahashi R.
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Journal Title
J Neurol.
Volume: 263
Issue: 9
Pages: 1719-26
DOI
Related Report
Peer Reviewed
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