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Identification and characterization of cell-to-cell transmissible alpha-synuclein seed

Research Project

Project/Area Number 16K21283
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
General anatomy (including histology/embryology)
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Katsutoshi Taguchi  京都府立医科大学, 医学(系)研究科(研究院), 助教 (60462701)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsα-Synuclein / prion-like propagation / seed / Parkinson's disease / プリオン様伝播モデル / α-シヌクレイン / Fibril / Seed構造 / パーキンソン病 / Lewy bodies / Seed / Cell-cell transmission / alpha-Synuclein / neurodegeneration / toxic oligomer
Outline of Final Research Achievements

α-Synuclein (αSyn) is one of major components of Lewy bodies and Lewy Neurites, the well-known pathological hallmarks of synucleinopathies including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). According to recent studies, cell-to-cell transmission of pathological αSyn in the brain is critical event for neurodegeneration. However, biochemical properties of these pathological molecules remain to be elucidated. Here, we isolated some characteristic αSyn-oligomers derived from preformed fibrils of αSyn. Next, we further recovered extracellular αSyn-oligomers having an uniform molecular mass in Native-PAGE from pathogenic conditioned culture medium. These oligomers successfully induced LB-pathology in cultured hippocampal neurons. Now, we are characterizing the pathogenic species of αSyn. These molecules will be a better target to inhibit the disease propagation via cell-to-cell transmission in PD and DLB.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (14 results)

All 2018 2017 2016 Other

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

  • [Journal Article] HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis.2017

    • Author(s)
      Watanabe Y, Tsujimura A, Taguchi K, Tanaka M.
    • Journal Title

      Autophagy

      Volume: 13 Issue: 1 Pages: 133-148

    • DOI

      10.1080/15548627.2016.1248018

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Brain region-dependent differential expression of alpha-synuclein.2016

    • Author(s)
      Taguchi K, Watanabe Y, Tsujimura A, Tanaka M.
    • Journal Title

      J Comp Neurol.

      Volume: 524 Issue: 6 Pages: 1236-58

    • DOI

      10.1002/cne.23901

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 神経細胞間伝播性α-シヌクレインの分離・同定とその解析2018

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      第123回 日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経解剖学を基盤としたパーキンソン病責任分子α-シヌクレインの機能解析2018

    • Author(s)
      田口勝敏
    • Organizer
      第123回 日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] パーキンソン病関連分子α-シヌクレインを高発現するマウス嗅球傍糸球体細胞の解析2017

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      第122回日本解剖学会総会・全国学術集会
    • Place of Presentation
      長崎県長崎市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] パーキンソン病関連分子α-シヌクレインを高発現するマウス嗅球傍糸球体細胞の解析2017

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      第122回 日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characterization of α-synuclein-enriched periglomerular cells in the mouse olfactory bulb2017

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      第40回 日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] パーキンソン病関連分子α-シヌクレインを高発現する嗅球傍糸球体細胞の解析2017

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      第93回 日本解剖学会学術集会・近畿支部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞内αシヌクレイン凝集体の形成/分解サイクルと細胞生存への影響について2016

    • Author(s)
      辻村敦、渡邊義久、田口勝敏、田中雅樹
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Characterization of alpha-synuclein-enriched periglomerular cells in the ojfactory bulb2016

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      北米神経科学会 SfN2016
    • Place of Presentation
      米国 サンディエゴ
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of α-synuclein-enriched periglomerular cells in the mouse olfactory bulb2016

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] パーキンソン病関連分子α-シヌクレインを高発現する嗅球傍糸球体細胞の解析2016

    • Author(s)
      田口勝敏、渡邊義久、辻村敦、田中雅樹
    • Organizer
      第92回 日本解剖学会学術集会・近畿支部会
    • Place of Presentation
      大阪府狭山市
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都府立医科大学 生体構造科学 教室ホームページ

    • URL

      http://www.f.kpu-m.ac.jp/k/anatomy1/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 京都府立医科大学 生体構造科学

    • URL

      http://www.f.kpu-m.ac.jp/k/anatomy1/

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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