Autophagy-mediated tau pathology formation and propagation
| Project/Area Number |
16K19057
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka City University |
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Principal Investigator |
Umeda Tomohiro 大阪市立大学, 大学院医学研究科, 助教 (70549790)
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ドラッグリポジショニング / タウ / リファンピシン / オートファジー / tau / 伝播 / 神経変性疾患 / 認知症 / アルツハイマー病 / 老化 |
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| Outline of Final Research Achievements |
In this study, we found that intracellular tau aggregation was associated by selective-autophagy chaperon p62. P62-mediated tau aggregates were secreted to extracellular space depend on autophagy activity. And we succeeded in the generation of tau pathology transmission model based on our WT htau-Tg mouse. Furthermore, we found that the well-known drug “rifampicin” works as the autophagy restoration agent and the intranasal administration of rifampicin shows highly protective effects on the phenotypes of Alzheimer’s disease model mouse.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で見出されたオートファジーのタウ病理形成への影響と、これらを抑制可能なrifampicinの薬効の発見は、既存医薬品のdrug-repositioningの有用性を示すとともに、他因子疾患ともいえる認知症に対してrifampicinが単剤でカクテル療法同等の効果を発揮可能であることを示している。今後臨床試験を経て、適応の拡大による臨床現場での使用を実現したい。
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Report
(4 results)
Research Products
(5 results)
