| Project/Area Number |
18K15359
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Tarutani Airi 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (10815187)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | プリオン様伝播 / 神経変性疾患 / αシヌクレイン / プリオン / strain(株) / シヌクレイノパチー / 株(strain) / 細胞間伝播 |
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| Outline of Final Research Achievements |
The concept that abnormal protein aggregates show prion-like propagation between cells has been considered to explain the onset and progression of many neurodegenerative diseases. Indeed, both synthetic amyloid-like fibrils and pathogenic proteins extracted from patients’ brains induce self-templated amplification and cell-to-cell transmission in vitro and in vivo. We investigated in detail the prion-like seeding activities of pathogenic α-synuclein(α-syn) extracted from patients with α-synucleinopathy. Pathogenic α-syn seeds derived from dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) showed structurally and biochemically distinct prion-like properties. Moreover, pathogenic α-syn derived from MSA exhibited higher seeding activity than those derived from DLB in cultured cells and wild-type mouse brains. These results indicate the presence of α-syn strains in α-synucleinopathy.
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| Academic Significance and Societal Importance of the Research Achievements |
神経変性疾患における臨床的、病理学的多様性はプリオンの性質の１つである異なる高次構造をもつ異常型タンパク質の”strains”(株)で説明可能である。本研究ではαシヌクレイノパチー患者脳から抽出した病原性シードを網羅的に用いることにより、αシヌクレインのstrainにおけるプリオン様性質の違いが明らかとなり、患者脳シードを用いたプリオン様伝播実験モデルの有用性が示された。
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