The propagation of tau oligomers and the neurotoxicity
Project/Area Number |
17K10297
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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 |
Psychiatric science
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Research Institution | Kyoto University |
Principal Investigator |
keiko Imamura 京都大学, iPS細胞研究所, 特定拠点講師 (90379652)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | タウ / タウオリゴマー / 前頭側頭葉変性症 / iPS細胞 / 神経活動 / FTLD / オリゴマー |
Outline of Final Research Achievements |
Abnormal tau protein aggregation along with cerebral atrophy is important pathological characteristics in the brains of Alzheimer's disease and frontotemporal dementia. In this study, we focused on the neurotoxicity of tau oligomers and their propagation. Extracellular tau oligomers caused neurotoxicity in neurons derived from FTLD-patient iPS cells, and the results indicated that the toxicity was propagated in a neural activity-dependent manner. Furthermore, we identified compounds that inhibited tau oligomer accumulation and neuronal cell death. We also reported that an intranasal tau vaccine was effective in FTLD mouse model. We explored potential therapeutic approaches based on the neurotoxic mechanisms of tau oligomers and their propagation.
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Academic Significance and Societal Importance of the Research Achievements |
タウタンパク質の折り畳み異常が、タウタンパク質凝集の早期段階であると考えられ、特に複数個のタウタンパク質が凝集して形成されるタウオリゴマーが強い神経毒性を有していると考えられている。本研究では、タウオリゴマーが、どのように神経毒性を発揮し、細胞から細胞への毒性伝搬に関連しているかを明らかにした。また、候補化合物やワクチンの有効性を見出し、タウオリゴマーの伝搬と神経毒性メカニズムに基づく治療アプローチの可能性を示した。本研究は超少子高齢社会における高齢者の認知症予防に貢献し、医学的・社会経済的にも高度の意義を有すると考えられる。
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Report
(4 results)
Research Products
(6 results)