The analysis of regulatory mechanisms of degradation/aggregation of abnormally accumulated protein in fontotemporal dementia brain.

• Project/Area Number: 24390283
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: TAKEDA Masatoshi 大阪大学, 医学(系)研究科(研究院), 教授 (00179649)
• Co-Investigator(Kenkyū-buntansha): TANAKA Toshihisa 大阪大学, 医学(系)・研究科(研究院), 准教授 (10294068) ; KUDO Takashi 大阪大学, 保健センター, 教授 (10273632) ; MORIHARA Takashi 大阪大学, 医学(系)・研究科(研究院), 助教 (90403196)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: タウ蛋白 / XIAP / アポトーシス / ＸＩＡＰ

Outline of Final Research Achievements

The effects of phosphorylation on interaction of tau with ubiquitin conjyugating enzyme XIAP (X-linked Inhibitor to apoptosis protein) were analayzed. Wild typed tau and Met-deleted tau were prepared and pull-down assay was caried out using XIAP after phophorylation of both tau and both tau proteins were incubated with ubiquitination enzyme sources togather with XIAP, and the effects of phosphorylation on ubiquitinaation were evaluated. No signifivcant difference was observed between non-phosphorylated samples and phosphorylated ones. Then binding partner to phosphorylated TDP-43 was invesytigated employing phosphorylated and non-phosphorylated peptides coresponding to Ser409/Ser410 of TDP-43. Then specigfic binding proteins were purified.

Research Products

• [Journal Article] アルツハイマー病の新規薬物の開発と臨床応用の可能性 (2015)
  • Author(s): 田中稔久、武田雅俊
  • Journal Title: 精神科治療学 Volume: 30 Pages: 63-70
• [Journal Article] γ-secretase modulators and presenilin 1 mutants act differently on presenilin/γ-secretase function to cleave Aβ42 and Aβ43. (2013)
  • Author(s): Okochi M, Tagami S, Yanagida K, Takami M, Kodama TS, Mori K, Nakayama T, Ihara Y, Takeda M.
  • Journal Title: Cell Rep. Volume: 3 Issue: 1 Pages: 42-51
  • DOI: 10.1016/j.celrep.2012.11.028
  • Peer Reviewed
• [Journal Article] Alzheimer disease and tau protein. (2012)
  • Author(s): Tanaka T, Maruyama D, TakedaM
  • Journal Title: Rinsho Shinkeigaku Volume: 52 Pages: 1171-1173
  • NAID: 130004505095
• [Journal Article] アミロイド沈着、神経原線維変化と認知機能低下 (2012)
  • Author(s): 田中稔久、武田雅俊
  • Journal Title: 老年精神医学雑誌 Volume: 23 Pages: 434-440
• [Journal Article] 認知症の薬理学的理解と臨床への活用 臨床精神薬理 (2012)
  • Author(s): 田中稔久、武田雅俊
  • Journal Title: 臨床精神薬理 Volume: 15 Pages: 1285-1296
• [Journal Article] アルツハイマー病の薬物療法の展開 (2012)
  • Author(s): 田中稔久、武田雅俊
  • Journal Title: 臨床精神医学 Volume: 41 Pages: 1681-1691
• [Presentation] 認知症におけるタウの分子病理 (2014)
  • Author(s): 田中稔久
  • Organizer: 第20回近畿老年期認知症研究会
  • Place of Presentation: リーガロイヤルNCB（大阪）
  • Year and Date: 2014-07-05
  • Invited
• [Presentation] N-terminal modification of tau regulates its degradation. (2013)
  • Author(s): Tanaka T, Maruyama D, Sato M, Terada M, Takeda M.
  • Organizer: Alzheimer's Association International Conference (AAIC2013), Boston, U.S.A., July 13-18(17), 2013.
  • Place of Presentation: Boston, USA.
• [Presentation] Phosphorylation of tau at Ser214 regulates degradation process of tau. (2012)
  • Author(s): Tanaka T, Maruyama D, Takeda M
  • Organizer: Alzheimer's Association International Conference (AAIC2012)
  • Place of Presentation: Vancouver (Canada)
  • Year and Date: 2012-07-17
• [Presentation] アルツハイマー病とタウ蛋白 シンポジウム「アルツハイマー病の新展開-分子病態から治療戦略へ New Development for Alzheimer's Diseas←From Molecular Pathogenesis to Therapeutic Strategy」 (2012)
  • Author(s): 田中稔久
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム(東京)(招待講演)
  • Year and Date: 2012-05-24