• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Sensitive detection of abnormal prion protein in genetic human prion diseases

Research Project

Project/Area Number 23300127
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionNagasaki University

Principal Investigator

ATARASHI Ryuichiro  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (90452846)

Co-Investigator(Renkei-kenkyūsha) NISHIDA Noriyuki  長崎大学, 医歯薬学総合研究科(医学系), 教授 (40333520)
SATOH Katsuya  長崎大学, 医歯薬学総合研究科(医学系), 准教授 (70398147)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords神経変性疾患 / 遺伝性プリオン病 / プリオン病 / 異常型PrP / real-time QUIC法 / 髄液検査 / FK506 / 予防・治療法
Outline of Final Research Achievements

The genetic form of human Prion diseases (gPrD) is caused by mutations in the prion protein gene. We recently developed a highly sensitive amplification technology, designated real-time quaking-induced conversion (RT-QUIC). In this study, we evaluated RT-QUIC assay in patients with gPrD, as a diagnostic tool. The detection sensitivities of RT-QUIC were as follows: GSS(78%), FFI(100%), gCJD E200K(87%). In contrast, the detection sensitivities of biomarkers were considerably lower: GSS(11%), FFI(0%), gCJD E200K(73%). Thus, RT-QUIC had a much higher detection sensitivity compared with testing for biomarkers. Moreover, we evaluated the effect of FK506 on prion infection, using cell culture and animal models. We found that FK506 reduced PrPSc and increased the formation of autolysosome in prion-infected cells. The survival periods in prion-inoculated mice were significantly increased when FK506 was administered. These findings show that FK506 could constitute a novel anti-prion drug.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 5 results) Presentation (7 results) (of which Invited: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Increased expression of p62/SQSTM1 in prion diseases and its association with2014

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

      Sci Rep.

      Volume: 4 Issue: 1 Pages: 4504-4504

    • DOI

      10.1038/srep04504

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features of genetic Creutzfeldt-Jakob disease with V180I mutation in the prion protein gene.2014

    • Author(s)
      Qina, T., N. Sanjo, M. Hizume, M. Higuma, M. Tomita, R. Atarashi, K. Satoh, I. Nozaki, T. Hamaguchi, Y. Nakamura, A. Kobayashi, T. Kitamoto, S. Murayama, H. Murai, M. Yamada and H. Mizusawa
    • Journal Title

      BMJ Open

      Volume: 4 Issue: 5 Pages: e004968-e004968

    • DOI

      10.1136/bmjopen-2014-004968

    • NAID

      120006986552

    • Related Report
      2014 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pressure-assisted dissociation and degradation of "proteinase K-resistant" fibrils prepared by seeding with scrapie-infected hamster prion protein.2014

    • Author(s)
      Akasaka K, Maeno A, Murayama T, Tachibana H, Fujita Y, Yamanaka H, Nishida N, Atarashi R.
    • Journal Title

      Prion

      Volume: 8(4) Issue: 4 Pages: 314-318

    • DOI

      10.4161/pri.32081

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FK506reduces abnormal prion protein through the activation of autolysosomal degradation and prolongs survival in prion-infected mice.2013

    • Author(s)
      Nakagaki T, Satoh K, Ishibashi D, Fuse T, Sano K, Kamatari YO, Kuwata K, Shigematsu K, Iwamaru Y, Takenouchi T, Kitani H, Nishida N, Atarashi R.
    • Journal Title

      Autophagy.

      Volume: 9 Issue: 9 Pages: 1386-1394

    • DOI

      10.4161/auto.25381

    • NAID

      120006986076

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Age-Dependent Impairment of Eyeblink Conditioning in Prion Protein-Deficient Mice2013

    • Author(s)
      Kishimoto Y, Hirono M, Atarashi R, Sakaguchi S, Yoshioka T, Katamine S, Kirino
    • Journal Title

      PLoS One.

      Volume: 8 Issue: 4 Pages: e60627-e60627

    • DOI

      10.1371/journal.pone.0060627

    • NAID

      120006985917

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early Detection of Abnormal Prion Protein in Genetic Human Prion Diseases Now Possible Using Real-Time QUIC Assay.2013

    • Author(s)
      Sano K, Satoh K, Atarashi R, Takashima H, Iwasaki Y, Yoshida M, Sanjo N, Murai
    • Journal Title

      PLoS One

      Volume: 8(1) Issue: 1 Pages: e54915-e54915

    • DOI

      10.1371/journal.pone.0054915

    • NAID

      120006985758

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective role of MyD88 independent innate immune responses against prion infection.2012

    • Author(s)
      Ishibashi D, Atarashi R, Nishida N
    • Journal Title

      Prion

      Volume: 6(5) Issue: 5 Pages: 43-446

    • DOI

      10.4161/pri.22579

    • NAID

      120006985798

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multicentre multiobserver study of diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease : a reliability and agreement study2012

    • Author(s)
      Fujita K, Harada M, Sasaki M, Yuasa T, Sakai K, Hamaguchi T, Sanjo N, Shiga Y, Satoh K, Atarashi R, Shirabe S, Nagata K, Maeda T, Murayama S, Izumi Y, Kaji R, Yamada M, Mizusawa H
    • Journal Title

      BMJ Open

      Volume: 2(1)

    • NAID

      120006864094

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective role of interferon regulatory factor3-mediated signaling against prion infection2012

    • Author(s)
      Ishibashi D, Atarashi R, Fuse T, Nakagaki T, Yamaguchi N, Satoh K, Honda K, Nishida N
    • Journal Title

      J Virol

      Volume: (Epub ahead of print)

    • NAID

      120006985559

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High sensitivity of an ELISA kit for detection of the gamma-isoform of 14-3-3 proteins : usefulness in laboratory diagnosis of human prion disease2011

    • Author(s)
      Matsui Y, Satoh K, Miyazaki T, Shirabe S, Atarashi R, Mutsukura K, Satoh A, Kataoka Y, Nishida N
    • Journal Title

      BMC Neurol

      Volume: 11 Pages: 120-120

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-time quaking-induced conversion : A highly sensitive assay for prion detection2011

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

      Prion

      Volume: 5(3) Pages: 150-153

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Clinical usefulness of the in vitro amplification of prion amyloid formation.2014

    • Author(s)
      Atarashi R
    • Organizer
      JSPS Japan Hungary Joint Seminar
    • Place of Presentation
      大阪(大阪大学)
    • Year and Date
      2014-11-18 – 2014-11-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 異常型プリオンタンパク試験管内増幅法(Real-time QUIC法)によるプリオン株鑑別診断法の開発と分子機構の解明2014

    • Author(s)
      新竜一郎, 祖母井香織, 福田茂夫,西田教行
    • Organizer
      第62回日本ウイルス学会学術集会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 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, Nishida N
    • Organizer
      Prion2014
    • Place of Presentation
      Trieste, Italy
    • Year and Date
      2014-05-27 – 2014-05-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] RT-QUIC法を用いたヒトプリオンサンプル中のSeeding Activityの測定2012

    • Author(s)
      高月英恵、新竜一郎、佐野和憲、佐藤克也、西田教行
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Evaluation of RT-QUIC (real-time quaking-induced conversion) assay for genetic human prion diseases2011

    • Author(s)
      新竜一郎
    • Organizer
      CJD 2011 and the Ninth Annual CJD Foundation Family Conference
    • Place of Presentation
      アメリカ合衆国(ワシントンDC)
    • Year and Date
      2011-07-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Evaluation of RT-QUIC (real-time quaking-induced conversion) assay for genetic human prion diseases2011

    • Author(s)
      新竜一郎
    • Organizer
      Prion2011
    • Place of Presentation
      カナダ(モントリオール)
    • Year and Date
      2011-05-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] プリオン蛋白の構造安定性に対する金属イオンの影響

    • Author(s)
      祖母井香織, 新竜一郎, 西田教行
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Annual Research Report
  • [Book] Annual Review神経「プリオン病の髄液診断の可能性」2011

    • Author(s)
      新竜一郎、佐藤克也
    • Publisher
      中外医学社
    • Related Report
      2011 Annual Research Report
  • [Remarks] 長崎大学大学院医歯薬学総合研究科感染分子解析学ホームページ

    • URL

      http://www.med.nagasaki-u.ac.jp/mmi/cmb/

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.med.nagasaki-u.ac.jp/mmi/cmb/index.html

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi