The role and mechanisms of TORC and HDAC signaling pathway and therapeutic new-class small compounds for neurological disease
| Project/Area Number |
24390222
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
sasaki tsutomu 大阪大学, 医学部附属病院, 助教 (20534879)
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| Co-Investigator(Kenkyū-buntansha) |
kitagawa kazuo 東京女子医科大学, 医学部, 教授 (70301257)
nagaoka yasuo 関西大学, 工学部, 教授 (90243039)
takemori hiroshi 国立研究開発法人医薬基盤, 健康・栄養研究所, プロジェクトリーダー (90273672)
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| Co-Investigator(Renkei-kenkyūsha) |
mochiduki hideki 大阪大学, 医学系研究科, 教授 (90230044)
uesato shinnichi 関西大学, 工学部, 教授 (50111969)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | 脳虚血 / シグナルトランスダクション / ＣＲＥＢ / ＳＩＫ（塩誘導性キナーゼ） / ＨＤＡＣ（ヒストン脱アセチル化酵素） / パーキンソン病 / ＨＤＡＣ阻害剤 / 創薬 / CRTC / SIK（塩誘導性キナーゼ） / HDAC / アポトーシス / CREB / エピゲノム / TORC / 低分子化合物 / 神経疾患 / 脳卒中 |
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| Outline of Final Research Achievements |
Although patients suffering from neurological disease including both neurodegenerative disease and stroke will increase dramatically in the coming years, there are currently a few effective drugs for neuronal protection and disease-modifying therapy. To provide new therapies to overcome these disease, we have examined both roles and mechanisms of salt-inducible kinase (SIK)-CREB-CRTC signaling and both histone deacetylases (HDACs) - histone acetylation. These cascade has been attributed to both not only neuronal injury but also inflammation in many neurological diseases. Among the original HDAC inhibitor library, we identified a novel HDAC1/2 isoform-specific inhibitor for Parkinson's disease and stroke. The isoform selective inhibition of HDAC may pave the way to new strategies for neurological disease.
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Report
(5 results)
Research Products
(40 results)
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[Journal Article] Discovery of new low-molecular-weight p53-Mdmx disruptors and their anti-cancer activities2016
Author(s)
Uesato, S.; Matsuura, Y.; Matsue, S.; Sumiyoshi, T.; Hirata, Y.; Takemoto, S.; Kawaratani, Y.; Yamai, Y.; Ishida, K.; Sasaki, T.; Enari, M.
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Journal Title
Bioorg Med Chem.
Volume: 24
Pages: 1919-1926
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line.2014
Author(s)
Ayako Kumagai, Akira Fujita, Tomoki Yokoyama, Yuki Nonobe, Yasuhiro Hasaba, Tsutomu Sasaki, Yumi Itoh, Minako Koura, Osamu Suzuki, Shigeki Adachi, Haruko Ryo, Arihiro Kohara, Lokesh P. Tripathi, Masato Sanosaka, Toshiki Fukushima, Taisei Nomura, Hiroshi Takemori, et al.
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Journal Title
Genes (Basel).
Volume: 5
Pages: 1095-1114
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice2012
Author(s)
Uebi T, Itoh Y, Hatano O, Kumagai A, Sanosaka M, Sasaki T, Sasagawa S, Doi J, Tatsumi K, Mitamura K, Morii E, Aozasa K, Kawamura T, Okumura M, Nakae J, et al.
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Journal Title
DOI
Related Report
Peer Reviewed
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[Journal Article] Suppression of dynamin GTPase decreases alpha-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy.2012
Author(s)
Konno M, Hasegawa T, Baba T, Miura E, Sugeno N, Kikuchi A, Fiesel FC, Sasaki T, Aoki M, Itoyama Y, Takeda A.
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Journal Title
J. Neurol.
Volume: 7
Pages: 315-317
DOI
Related Report
Peer Reviewed
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[Presentation] Efficacy and implications of isoform selective Histone deacetylase inhibitors for cerebral ischemia2016
Author(s)
Sasaki T, Chonng Chi-Jing, Watanabe A, Kanki H, Yukami T, Hayakawa H, Yasuda T, Baba K, Sakaguchi M, Uesato S, Mochizuki H
Organizer
第57回日本神経学会学術大会
Place of Presentation
神戸
Year and Date
2016-05-18
Related Report
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[Presentation] Efficacy and implications of selective class I or II Histone deacetylase inhibitors for ischemic brain injury.2014
Author(s)
Sasaki T, Choong CJ, Watanabe A, Hirata Y, Sanosaka M, Yukami T, Kitagawa K, Takemori H, Uesato S, Mochizuki H.
Organizer
American Neurological Association's 2014 Annual Meeting
Place of Presentation
Baltimore Marriott Waterfront Hotel, Maryland, USA
Year and Date
2014-10-12
Related Report
Int'l Joint Research
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