Drug Discovery of Alzheimer Disease from Molecules- RegulatingMicrotubule Polymerization

2010 Fiscal Year Self-evaluation Report

• Project/Area Number: 20228006
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Applied molecular and cellular biology
• Research Institution: Tohoku University
• Principal Investigator: UCHIDA Takafumi Tohoku University, 大学院・農学研究科, 教授 (80312239)
• Project Period (FY): 2008-05-12 – 2013-03-31
• Keywords: アルツハイマー病 / 微小管重合 / 微小管関連タンパク質 / 機能調節剤 / プロリン異性化酵素

Research Abstract

脳神経に特異的に存在し、微小管の重合を促進するタンパク質であるタウは、過剰なリン酸化をうけ、変性・凝集し、アルツハイマー病(AD)の原因になると考えられてきたが、我々は、ADの本質的な病因は、タウではなくて微小管重合の低下だと考えた。
本研究では、第一にこの仮説の妥当性を検討し、第二に、微小管重合制御蛋白質の同定と作用機構の解明し、第三に、この仮説に基づき、AD型認知症の予防・治療に効果のある薬剤や飲食料品を発見することである。

Research Products

• [Journal Article] Prolyl isomerase Pinl protects mice from endotoxin shock (2011)
  • Author(s): Akiyama H, Misawa T, Ono M, Uchida C, Uchida T
  • Journal Title: PLoS One Pages: e14656
  • Peer Reviewed
• [Journal Article] A dual inhibitor against prolyl isomerase Pinl and cyclophilin discovered by a novel real-time fluorescence detection method. (2011)
  • Author(s): Mori, T, Hidaka M, Lin Y, Yoshizawa I, Okabe T, Egashira S, Kojima H, Nagano T, Koketsu M, Takamiya, M, Uchida T
  • Journal Title: Biochem.Biophys.Res.Commun. 406 Pages: 439-443
  • Peer Reviewed
• [Journal Article] Direct Optical Microscopic Observation of the Microtubule Polymerization Intermediate Sheet Structure in the Presence of Gas7. (2009)
  • Author(s): Uchida T, Akiyama H, Sakamoto W, Koga T, Yan, K., Uchida C, Hirose K, Itoh JT
  • Journal Title: J Mol Biol 391 Pages: 849-857
  • Peer Reviewed
• [Journal Article] hGas7b that promotes tubulin polymerization is decreased in Alzheimer's disease brain. (2009)
  • Author(s): Akiyama H, Gotoh A, Shin RW, Koga T, Ohashi T, Sakamoto W, Arai H, Harada A, Sawa A, Uchida C, Uchida T
  • Journal Title: J Biol Chem 284 Pages: 32695-32699
  • Peer Reviewed
• [Journal Article] The peptidyl-prolyl isomerase Pinl determines parathyroid hormone mRNA levels and stability in secondary hyperparathyroidism. (2009)
  • Author(s): Nechama M, Uchida T, Yosef-Levi IM, Silver J, Naveh-Many T
  • Journal Title: J Clin Invest 119 Pages: 3103-3114
  • Peer Reviewed
• [Presentation] hGas7b Enhances Microtubule Polymerization but Blocks Kinesin Movement on Microtubule (2010)
  • Author(s): Masafumi Hidaka, Tomoe Koga, Aina Goto, Hideo Higuchi, Takafumi Uchida
  • Organizer: 4th Mechanobiology Workshop : Actin, The Cytoskeleton and the Nucleus
  • Place of Presentation: シンガポール
  • Year and Date: 2010-11-10
• [Presentation] 微小管重合制御因子の探索 (2010)
  • Author(s): 藤田彩子・甲賀友恵・後藤愛那・坂本渉・寺川貴裕・内田隆史
  • Organizer: 日本農芸化学会大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] Pinl阻害剤の探索系の確立 (2010)
  • Author(s): 吉澤いぶき・林宜瑾・坂場義正・多田羅洋太・須田義人・纐纈守・豊原治彦・塩見和朗・大村智・山下まり・森正・内田隆史
  • Organizer: 日本農芸化学会大会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-28
• [Presentation] Establishment of High-Throughput Screening for Prolyl Isomerasese Inhibitors with Real-time Fluorescence Monitoring System (2009)
  • Author(s): TADASHI MORI, SEIMA ITAMI, MARI TAKAMIYA, TSUTOMU KAMIYAMA, TAKAFUMI UCHIDA
  • Organizer: 16th SBS annual meeting
  • Place of Presentation: フェニックス、米国
  • Year and Date: 2009-04-11
• [Presentation] 微小管重合を調節するタンパク質および化学物質の探索 (2009)
  • Author(s): 坂本渉・林宜瑾・甲賀友恵・纐纈守・奥田徹・内田隆史
  • Organizer: 日本農芸化学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2009-03-28
• [Remarks] 研究室ホームページ
  • URL: http://www.agri.tohoku.ac.jp/enzyme/index-j.html