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The elucidation of molecular basis of the diversity and transmissibility in abnormal prion protein formation

Research Project

Project/Area Number 15H04269
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionUniversity of Miyazaki (2016-2018)
Nagasaki University (2015)

Principal Investigator

Atarashi Ryuichiro  宮崎大学, 医学部, 教授 (90452846)

Research Collaborator IMAMURA morikazu  
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywordsプリオン病 / プリオン株 / PrP / タンパク単独仮説 / 神経変性疾患 / リコンビナントタンパク / プリオンタンパク
Outline of Final Research Achievements

Accumulating evidence suggests that the continuous conversion of normal form of prion protein (PrPC) into abnormal form of PrP (PrPSc) in affected hosts plays a central role of the pathogenesis of prion diseases. However, the molecular basis of the diversity and transmissibility in PrPSc formation has not been well understood. Using the protein misfolding cyclic amplification (PMCA) technique, we found that some cofactors such as heparin sulfate or its analog heparin greatly enhanced the formation of PrPSc in vitro. Furthermore, we developed an advanced PMCA system using E-coli derived recombinant PrP as a substrate. We currently examined the diversity and transmissibility of the advanced PMCA products.

Academic Significance and Societal Importance of the Research Achievements

補助的因子を加えた試験管内異常化反応法により、これまで効率の低かったプリオン株(非典型牛海綿状脳症や慢性消耗病等)の高効率な変換が可能となった。またその補助的因子を加えることにより、大腸菌由来リコンビナントPrP(recPrP)を反応基質とした試験管内PrP異常化反応系において、そのプリオン株特有の産物を生成させることが初めて可能となった。これらの結果は、プリオン病の病態機構の理解を大きく進展させたと考えている。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (18 results)

All 2017 2016 2015 Other

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 2 results,  Open Access: 10 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Development of radioiodinated acridine derivatives for in vivo imaging of prion deposits in the brain.2017

    • Author(s)
      Kawasaki M, Fuchigami T, Kobashi N, Nakagaki T, Sano K, Atarashi R, Yoshida S, Haratake M, Nishida N, Nakayama M
    • Journal Title

      Bioorganic & Medicinal Chemistry.

      Volume: 25 Issue: 3 Pages: 1085-1093

    • DOI

      10.1016/j.bmc.2016.12.020

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Real-Time Quaking-Induced Conversion for Diagnosis of Prion Disease.2017

    • Author(s)
      Satoh K, Atarashi R, Nishida N.
    • Journal Title

      Methods Mol Biol.

      Volume: 1658 Pages: 305-310

    • DOI

      10.1007/978-1-4939-7244-9_21

    • ISBN
      9781493972425, 9781493972449
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A direct assessment of human prion adhered to steel wire using real-time quaking-induced conversion.2016

    • Author(s)
      Mori T, Atarashi R, Furukawa K, Takatsuki H, Satoh K, Sano K, Nakagaki T, Ishibashi D, Ichimiya K, Hamada M, Nakayama T, Nishida N.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 24993-24993

    • DOI

      10.1038/srep24993

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CSF RT-QuIC is a robust and reliable test for sporadic CJD: An international study.2016

    • Author(s)
      McGuire LI, Poleggi A, Poggiolini I, Suardi S, Grznarova K, Shi S, de Vil B, Sarros S, Satoh K, Cheng K, Cramm M, Fairfoul G, Schmitz M, Zerr I, Cras P, Equestre M, Tagliavini F, Atarashi R, Knox D, Collins S, Haik S, Parchi P, Pocchiari M, Green A.
    • Journal Title

      Ann Neurol.

      Volume: 未定 Issue: 1 Pages: 160-165

    • DOI

      10.1002/ana.24679

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structure-Based Drug Discovery for Prion Disease Using a Novel Binding Simulation.2016

    • Author(s)
      Ishibashi D, Nakagaki T, Ishikawa T, Atarashi R, Watanabe K, Cruz FA, Hamada T, Nishida N.
    • Journal Title

      EBioMedicine.

      Volume: 9 Pages: 238-249

    • DOI

      10.1016/j.ebiom.2016.06.010

    • NAID

      120006987627

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases.2016

    • Author(s)
      Schmitz M, Cramm M, Llorens F, Muller-Cramm D, Collins S, Atarashi R, Satoh K, Orru CD, Groveman BR, Zafar S, Schulz-Schaeffer WJ, Caughey B, Zerr I.
    • Journal Title

      Nat Protoc.

      Volume: 11 Issue: 11 Pages: 2233-2242

    • DOI

      10.1038/nprot.2016.120

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prion-Seeding Activity Is widely Distributed in Tissues of Sporadic Creutzfeldt-Jakob Disease Patients.2016

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

      EBioMedicine.

      Volume: 12 Pages: 150-155

    • DOI

      10.1016/j.ebiom.2016.08.033

    • NAID

      120006987618

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] 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] Structural conservation of prion strain specificities in recombinant prion protein fibrils in real-time quaking-induced conversion.2015

    • Author(s)
      Sano K, Atarashi R, Nishida N.
    • Journal Title

      Prion.

      Volume: 9 Issue: 4 Pages: 237-243

    • DOI

      10.1080/19336896.2015.1062201

    • 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] 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
  • [Presentation] バキュロウイルス-昆虫細胞発現組換えPrP を用いた試験管内変換系の構築に基づくプリオン変換・生成機構の解明.2017

    • Author(s)
      新竜一郎, 今村守一, 森剛志, 高月英恵, 岩丸祥史
    • Organizer
      日本薬学会第138年会(シンポジウム)
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Spontaneously-generated baculovirus-derived abnormal recombinant prion protein has infectivity.2017

    • Author(s)
      Imamura M, Tabeta N, Iwamaru Y, Yokoyama T, Murayama Y, Mori T, Takatsuki H, Atarashi R.
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Wire-QuIC reaction can detect abnormal human prion seeds from contaminated stainless steel-wire2016

    • Author(s)
      Mori T, Atarashi R, Satoh K,Ishibashi D, Nakagaki T, Nishida N.
    • Organizer
      第64回日本ウイルス学会学術集会
    • Place of Presentation
      札幌、日本
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] "Wire-QuIC": a new detection sysmte of human prion2016

    • Author(s)
      Mori T, Atarashi R, Takatsuki H, Satoh K, Nakagaki T, Ishibashi D, Nishida N.
    • Organizer
      Prion 2016
    • Place of Presentation
      東京、日本
    • Year and Date
      2016-05-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Diagnostic evaluation of real-time quaking-induced conversion for the detection of human prion diseases.2015

    • Author(s)
      Ryuichiro Atarashi
    • Organizer
      Asian Pacific Prion Symposium 2015
    • Place of Presentation
      石川県立音楽堂(石川県・金沢市)
    • Year and Date
      2015-09-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 宮崎大学ニュースリソース

    • URL

      http://www.miyazaki-u.ac.jp/newsrelease/edu-info/alprenolol.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

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