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Efficient seed-dependent alpha-synuclein aggregation in real-time quaking-induced conversion assay

Research Project

Project/Area Number 25640029
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
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) SATOH Katsuya  長崎大学, 医歯薬学総合研究科(保健学科), 教授 (70398147)
SANO Kazunori  福岡大学, 薬学部, 講師 (50534343)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsレビー小体型認知症 / alpha-synuclein / オリゴマー / アミロイドフィブリル / 神経変性疾患
Outline of Final Research Achievements

The molecular basis of seed-dependent aggregation of alpha-synuclein (aSyn) in the pathogenesis of dementia with Lewy bodies (DLB) remains unclear. We investigated whether brain tissues from DLB, which contain serine 129 (Ser129) phosphorylated insoluble aggregates of aSyn, can convert recombinant aSyn (r-aSyn) to amyloid fibrils using real-time quaking-induced conversion (RT-QUIC). Diffuse neocortical DLB type yielded 50% seeding dose (SD50) values of 107-8/g brain. The SD50 of Limbic DLB type was about 105/g brain. Further studies found that RT-QUIC assay was able to discriminate DLB from other neurodegenerative disorders. Of note, the seeding activity was reconstructed in reactions seeded with soluble r-aSyn oligomers, but not with insoluble r-aSyn aggregates, regardless its Ser129 phosphorylation status. These findings suggest that RT-QUIC using r-aSyn as a substrate can be applied to detect the pathogenic aSyn fibrils in DLB, and the potential culprit is oligomeric forms of aSyn.

Report

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

    (3 results)

All 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results)

  • [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 Research-status 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 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

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

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