The role and mechanisms of TORC and HDAC signaling pathway and therapeutic new-class small compounds for neurological disease

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390222
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Osaka University
• Principal Investigator: sasaki tsutomu 大阪大学, 医学部附属病院, 助教 (20534879)
• 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)
• 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)
• Project Period (FY): 2012-04-01 – 2016-03-31
• 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

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.

Free Research Field

神経内科学