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Identification of Alzheimer's disease-relevant neuronal death inhibiting molecular basis and its application for drug development

Research Project

Project/Area Number 25460343
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionTokyo Medical University

Principal Investigator

HASHIMOTO YUICHI  東京医科大学, 医学部, 講師 (00317330)

Co-Investigator(Renkei-kenkyūsha) MATSUOKA MASAAKI  東京医科大学, 医学部, 教授 (70222297)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアルツハイマー病 / 神経細胞死 / ヒューマニン / 創薬化学 / 細胞内シグナル伝達 / CLSP / UNC5C / アミロイド前駆体タンパク質 / Apollon / 神経科学
Outline of Final Research Achievements

In this research program, we have examined the neuronal cell death mechanism underlying Alzhemer’s disease (AD), identified of Humanin (HN), a secreted bioactive peptide factor against AD-relevant neurotoxicity, inducible signal molecules, and confirmed in vivo effect of calmodulin-like skin protein (CLSP) on scopolamine-induced amnesia.
The results were: (1) A598T-APP inhibited TGFbeta2/wild-type APP-induced neuronal death, (2) By differential display, we identified SH3BP5 and Apollon is mediator of HN-neuroprotective signals, and (3) recombinant CLSP, administered intracerebroventricularly or intraperitoneally, ameliorates scopolamine-induced dementia in mice.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (10 results)

All 2016 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] A mutation protective against Alzheimer's disease renders amyloid β precursor protein incapable of mediating neurotoxicity2014

    • Author(s)
      Hashimoto Y, Matsuoka M
    • Journal Title

      J Neurochem

      Volume: not decided Issue: 2 Pages: 291-300

    • DOI

      10.1111/jnc.12717

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Apollon/Bruce is upregulated by Humanin.2014

    • Author(s)
      4.Hashimoto, Y., Takeshita, Y., Naito, M., Uchino, H. and Matsuoka, M
    • Journal Title

      Mol Cell Biochem.

      Volume: 397 Issue: 1-2 Pages: 147-55

    • DOI

      10.1007/s11010-014-2182-4

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secreted calmodulin-like skin protein ameliorates scopolamine-induced memory impairment.2013

    • Author(s)
      Hayashi M, Tajima H, Hashimoto Y, Matsuoka M.
    • Journal Title

      NeuroReport

      Volume: 25 Issue: 9 Pages: 751-735

    • DOI

      10.1097/wnr.0b013e328362d9fe

    • NAID

      120005407941

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secreted calmodulin-like skin protein inhibits neuronal death in cell-based Alzheimer's disease models via the heterotrimeric Humanin receptor2013

    • Author(s)
      Hashimoto Y, Nawa M, Kurita M, Tokizawa M,Iwamatsu A, Matsuoka M
    • Journal Title

      Cell Death Dis

      Volume: 4 Issue: 3 Pages: 555-555

    • DOI

      10.1038/cddis.2013.80

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] SH3-binding protein 5 mediates the neuroprotective effect of the secreted bioactive peptide Humanin by inhibiting c-Jun NH2-teminal kinase2013

    • Author(s)
      Takeshita Y, Hashimoto Y, Nawa M, Uchino H, Matsuoka M
    • Journal Title

      J Biol Chem

      Volume: 288 Issue: 34 Pages: 24691-24704

    • DOI

      10.1074/jbc.m113.469692

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] An Alzheimer's disease-linked mutant T835M-UNC5C causes neuronal cell death by activating an intracellular death signal cascade.2016

    • Author(s)
      橋本祐一 外山由夏 松岡正明
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 会議センター
    • Year and Date
      2016-03-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] An Alzheimer's disease-linked mutant T835M-UNC5C causes neuronal cell death by activating an intracellular death signal cascade2015

    • Author(s)
      Yuchi Hashimoto Masaaki Matsuoka
    • Organizer
      Society for Neuroscience 2015, SfN's 45th Annual Meeting
    • Place of Presentation
      米国 シカゴ市
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Apollon/Bruce is upregulated by Humanin2014

    • Author(s)
      橋本祐一 竹下裕二 内藤幹彦 内野博之 松岡正明
    • Organizer
      第131回日本薬理学会関東部会
    • Place of Presentation
      東北大学
    • Year and Date
      2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] An anti-Alzheimer’s disease mutation makes amyloid precursor protein unable to mediate transforming growth factor β2-induced neurotoxicity2014

    • Author(s)
      Hashimoto Y, Matsuoka M.
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      東北大学
    • Related Report
      2013 Research-status Report
  • [Presentation] SH3-binding protein 5 mediates the neuroprotective effect of Humanin by inhibiting c-Jun NH2-terminal kinase2013

    • Author(s)
      Hashimoto Y, Takeshita Y, Nawa M, Uchino H, Matsuoka M.
    • Organizer
      Society for Neuroscience 43rd annual meeting 2013
    • Place of Presentation
      アメリカ合衆国カリフォルニア州サンディエゴ市
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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