Development of neurogenesis inducer for neurodegenerative disorders
| Project/Area Number |
16K01932
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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 |
Chemical biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 神経新生 / ダウン症 / シーズ探索 / 神経発達 / 化合物探索 |
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| Outline of Final Research Achievements |
Down syndrome (DS) is the most frequent genetic cause of intellectual disability, affecting one in 1,000 live births worldwide. DS is caused by the extra chromosome 21, the prenatal diagnosis of DS is now feasible. Yet, no therapy is currently available. We screened for neurogenesis inducers which can restore impaired proliferation of neural stem cells in DS/DS models and identified ALGERNON (altered generation of neurons) as an inhibitor against DYRK1A encoded in DS critical region of chromosome 21. Treatment of pregnant dams with ALGERNON normalized the morphological abnormal brain development, and most remarkably, impaired neurocognitive behaviors in DS-offspring. These data suggest that the neurogenic phenotype of DS can be prevented by ALGERNON prenatal therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病やアルツハイマー病、ハンチントン病、筋委縮性軸索硬化症（ALS）などの疾患は、脳あるいは脊髄における特定の神経細胞群が徐々に死ぬことで、運動・知覚などの脳の高次機能に異常をきたす。現在のところこれらの疾患に対する根本的治療は存在しない。このような神経変性疾患に対し、特定の低分子化合物により脳・脊髄内に存在する神経幹細胞の増殖を促して新しく神経細胞を産生し、新生した神経細胞に失われた脳の高次機能を代替させることができれば、新たな治療法へと繋がると期待される。また神経新生の低下は精神発達疾患においても示唆されており、本研究による低分子化合物シーズの開発は適用拡大が見込まれる。
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Report
(5 results)
Research Products
(16 results)
