| Project/Area Number |
23390082
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | 独立行政法人医薬基盤研究所 |
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Principal Investigator |
TAKEMORI Hiroshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (90273672)
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| Co-Investigator(Kenkyū-buntansha) |
HATANO Osamu 奈良県立医科大学, 医学部, 講師 (40164850)
KITAGAWA Kazuo 大阪大学, 医学系研究科, 准教授 (70301257)
NAGAOKA Yasuo 関西大学, 工学部, 教授 (90243039)
田端 俊英 富山大学, 大学院理工学研究科, 准教授 (80303270)
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| Co-Investigator(Renkei-kenkyūsha) |
KUMAGAI Ayako 独立行政法人医薬基盤研究所, 創薬基盤研究部, 特任研究員 (20455869)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2011: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | SIK / CREB / 転写 / 神経保護 / フラボノイド / 阻害剤 / CRTC1 / ｃAMPシグナル / 神経 / 化合物 / 活性酸素 / 認知症 |
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| Research Abstract |
We reported that SIK2-KO mice showed neuro-protective phenotypes after the ischemia-reperfusion operation. In addition, SIK2 regulates hair color by inhibiting melanogenesis. By using these phenotypes, we tried to indentify new compounds that are helpful to care ischemia-reperfusion damage in the brain. We screened compounds by an in vitro kinase assay and identified fisetin as a candidate for the SIK2 inhibitor. However, fisetin did not inhibit SIK2 actions in cultured cells. Interestingly, fisetin changed mouse hair color, and we found methoxy-fisetin in mouse feces. The synthesized methoxy-fisetin (4MF) inhibited SIK2 and acted as a neuro-protector after the glutamate treatment in primary neurons. 4MF-treated mice showed enhanced memory capacity. In addition to 4MF, we obtained some compounds that showed neuro-protective activities in an SIK2 dependent or independent manners.
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