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Establishment of anti prion therapy by autophagy inducers

Research Project

Project/Area Number 26860671
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionNagasaki University

Principal Investigator

NAKAGAKI Takehiro  長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (80722917)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsFK506 / プリオン病 / オートファジー / 神経変性疾患
Outline of Final Research Achievements

We focused on autophagy that is degradation pathway of abnormal prion protein (PrPSc) as a therapeutic target of prion diseases. Previously, we reported that FK506 can be a therapeutic agent by activating autophagy. The most known regulator of autophagy is mammalian Target Of Rapamycin(mTOR). Torin1 and Torin2 which inhibit mTOR are well known autophagy inducer. We compared the anti prion effect of autophagy inducers(FK506, Torin1 and Torin2).Whereas Torin 1 and Torin2 they are well known autophagy inducers decreased PrPSc by about 50% in autophagy sensitive prion strain (Fukuoka-1 strain) infected cells, they did not reduce PrPSc in autophagy resistant strain (22L strain) infected cells. On the other hand, FK506 reduced PrPSc by about 80% in the cells with both Fukuoka-1 and 22L strains. These results suggested that FK506 has anti-prion effect stronger than already known autophagy inducers.

Report

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

    (7 results)

All 2015 2014

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits.2015

    • Author(s)
      Fuchigami T, Yamashita Y, Kawasaki M, Ogawa A, Haratake M, Atarashi R, Sano K, Nakagaki T, Ubagai K, Ono M, Yoshida S, Nishida N, Nakayama M.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 18440-18440

    • DOI

      10.1038/srep18440

    • NAID

      120006987233

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ubiquitin-specific protease 14 modulates degradation of cellular prion protein.2015

    • Author(s)
      Homma T, Ishibashi D, Nakagaki T, Fuse T, Mori T, Satoh K, Atarashi R, Nishida N.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 11028-11028

    • DOI

      10.1038/srep11028

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strain-Dependent Effect of Macroautophagy on Abnormally Folded Prion Protein Degradation in Infected Neuronal Cells.2015

    • Author(s)
      Ishibashi D, Homma T, Nakagaki T, Fuse T, Sano K, Takatsuki H, Atarashi R, Nishida N.
    • Journal Title

      PLoS One.

      Volume: 10 Issue: 9 Pages: 0137958-0137958

    • DOI

      10.1371/journal.pone.0137958

    • NAID

      120006986825

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid and Quantitative Assay of Amyloid-Seeding Activity in Human Brains Affected with Prion Diseases.2015

    • Author(s)
      Takatsuki H, Satoh K, Sano K, Fuse T, Nakagaki T, Mori T, Ishibashi D, Mihara B, Takao M, Iwasaki Y, Yoshida M, Atarashi R, Nishida N.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 6 Pages: 0126930-0126930

    • DOI

      10.1371/journal.pone.0126930

    • NAID

      120006986998

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Persistent prion infection disturbs the function of Oct-1, resulting in the down-regulation of murine interferon regulatory factor-3.2014

    • Author(s)
      Homma T, Ishibashi D, Nakagaki T, Fuse T, Sano K, Satoh K, Atarashi R, Nishida N.
    • Journal Title

      Sci Rep

      Volume: 4 Issue: 1 Pages: 6006-6006

    • DOI

      10.1038/srep06006

    • NAID

      120006986450

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conformational properties of prion strains can be transmitted to recombinant prion protein fibrils in real-time quaking-induced conversion.2014

    • Author(s)
      Sano K, Atarashi R, Ishibashi D, Nakagaki T, Satoh K, Nishida N.
    • Journal Title

      J Virol

      Volume: 88(20) Issue: 20 Pages: 11791-11801

    • DOI

      10.1128/jvi.00585-14

    • NAID

      120006986372

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The comparison of anti-prion effect of autophagy inducers2015

    • Author(s)
      Takehiro Nakagaki
    • Organizer
      Asia Pasific Prion Symposium 2015
    • Place of Presentation
      石川県金沢市 石川音楽堂
    • Year and Date
      2015-09-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2017-05-10  

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