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Drug discovery research for Alzheimer's disease focused on molecular chaperone

Research Project

Project/Area Number 24590084
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionKeio University

Principal Investigator

HOSHINO Tatsuya  慶應義塾大学, 薬学部, 助教 (70457589)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsβアミロイド / アルツハイマー / 分子シャペロン / Heat shock protein / アルツハイマー病
Outline of Final Research Achievements

We here examined the effect of geranylgeranylacetone, an inducer of heat shock protein (HSP) 70 expression, on the Alzheimer’s disease (AD)-related phenotypes. Repeated oral administration of geranylgeranylacetone to APP23 mice for 9 months not only improved cognitive function but also decreased levels of amyloid-β peptide (Aβ), Aβ plaque deposition and synaptic loss. These outcomes were similar to those observed in APP23 mice genetically modified to overexpress HSP70. Although the repeated oral administration of geranylgeranylacetone did not increase the level of HSP70 in the brain, a single oral administration of geranylgeranylacetone significantly increased the level of HSP70 when Aβ was concomitantly injected directly into the hippocampus. Since geranylgeranylacetone has already been approved for use as an anti-ulcer drug and its safety in humans has been confirmed, we propose that this drug be considered as a candidate drug for the prevention of AD.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (5 results)

All 2014 2013 2012

All Journal Article (5 results) (of which Peer Reviewed: 5 results)

  • [Journal Article] Diclofenac p rotects cultured human corneal epithelial cells against hyperosmolarity and ameliorates corneal surface damage in a rat mode l of dry eye.2014

    • Author(s)
      Sawazaki R, Ishihara T, Usui S, Hayashi E, Tahara K, Hoshino T, Higuchi A, Nakamura S, Tsubota K, Mizushima T.
    • Journal Title

      Invest. Ophthalmol. Vis. Sci.

      Volume: 55 Pages: 2547-66

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of Alzheimer’s disease-related phenotypes by geranylgeranylacetone in mice.2013

    • Author(s)
      214. Hoshino, T., Suzuki, K., Matsushima, T., Yamakawa, N., Suzuki, T. and Mizushima, T.
    • Journal Title

      PLoS One

      Volume: 8

    • NAID

      120005365906

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improvement of cognitive function in Alzheimer’s disease model mice by genetic and pharmacological inhibition of the EP4 receptor.2012

    • Author(s)
      Hoshino.T.et al.
    • Journal Title

      J. Neurochem.

      Volume: 120 Pages: 795-805

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Purification and characterization of hsp-inducers from eupatorium lindleyanum2012

    • Author(s)
      Yamashita. Y. et al.
    • Journal Title

      Biochem. Pharmacol.

      Volume: 82 Pages: 909-922

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppression of UV-induced wrinkle formation by induction of HSP70 expression in mice.2012

    • Author(s)
      Matsuda. M. et al.
    • Journal Title

      J. Invest. Dermatol.

      Volume: 133 Pages: 919-928

    • Related Report
      2012 Research-status Report
    • Peer Reviewed

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Published: 2013-05-31   Modified: 2019-07-29  

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