| Project/Area Number |
24241076
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NINOMIYA Kensuke 京都大学, 医学研究科, 助教 (00437279)
HOSOYA Takamitsu 東京医科歯科大学, 生体材料工学研究所, 教授 (60273124)
KATAOKA Naoyuki 京都大学, 大学院医学研究科, 准教授 (60346062)
TAKEUCHI Akihide 京都大学, 大学院医学研究科, 准教授 (90436618)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000)
Fiscal Year 2014: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
Fiscal Year 2013: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2012: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
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| Keywords | タウオパチー / アルツハイマー病 / 化合物 / スクリーニング / タウ / リン酸化酵素 / 急性ストレス / 神経変性疾患 / アルツハイマー / FTDP-17 / ストレス / 細胞 / DYRK1A / 低分子化合物 / ハイスループット |
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| Outline of Final Research Achievements |
Aberrant accumulation of TAU has been recognized as one of characteristic features in neurodegenerative diseases known as tauopathies, which include Alzheimer's disease. Deletion of Tau-encoding Mapt in mice prevented Amyloid-beta-mediated deficits, suggesting that reducing Tau protein confers resistance to Amyloid-beta-mediated neurodegeneration. In this study, we developed a cell-based assay system based on doxycycline-driven bicistronic expression of mCherry and TAU fused with EGFP, in order to evaluate effects of molecules on TAU protein. We identified a small molecule that induces degradation of TAU. This compound, FIT-068, decreased not only endogenous, but also mutant TAU proteins harboring genetic mutations of hereditary tauopathies. FIT-068-mediated decrease of TAU was prevented by pre-treatment with an inhibitor of lysosomal degradation, suggesting that FIT-068 induces autophagy-mediated degradation of TAU. FIT-068 is thus a promising drug candidate for treating tauopathies.
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