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In vivo analysis of prion-like conversion and transmission of alpha-Synuclein

Research Project

Project/Area Number 15K19502
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionTokyo Metropolitan Institute of Medical Science (2016-2017)
Osaka University (2015)

Principal Investigator

SUZUKI Mari  公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 主任研究員 (20455405)

Research Collaborator NAGAI Yoshitaka  大阪大学, 大学院医学系研究科・神経難病認知症探索治療学寄附講座, 教授
SAKAI Ryusuke  大阪大学, 大学院医学系研究科・神経内科/神経難病認知症探索治療学寄附講座, 大学院生
OBA Masaki  公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研修生
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsパーキンソン病 / レビー小体型認知症 / αシヌクレイン / ショウジョウバエ / 脂質 / ライソソーム病
Outline of Final Research Achievements

In sporadic PD and DLB, normally harmless αSyn proteins without any mutations might gain toxic functions by unknown mechanisms. Thus, it is important to elucidate the factors promoting the toxic conversion of αSyn. This study is aimed to explore the lipids that promote αSyn prion-like toxic conversion by using in vitro biochemical assay and Drosophila model. We found that several lipids accelerate the conversion of αSyn, and that one of the lipids found in vitro assay promote the toxicity of αSyn in fly model of PD. In addition, we established novel αSyn brain-transmission model fly that enables to monitor αSyn transmission in vivo and could be used to explore the molecular mechanism of αSyn prion-like transmission.

Report

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

    (22 results)

All 2018 2017 2016 2015 Other

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] A spontaneously immortalized Schwann cell line from aldose reductase-deficient mice as a useful tool for studying polyol pathway and aldehyde metabolism.2018

    • Author(s)
      2.Niimi N, Yako H, Takaku S, Kato H, Matsumoto T, Nishito Y, Watabe K, Ogasawara S, Mizukami H, Yagihashi S, Chung SK, Sango K.
    • Journal Title

      Journal of Neurochemistry

      Volume: 印刷中 Pages: 97-106

    • DOI

      10.1016/j.neuint.2017.12.014

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2018

    • Author(s)
      Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
    • Journal Title

      Hum Mol Genet.

      Volume: 27 Issue: 5 Pages: 823-836

    • DOI

      10.1093/hmg/ddy003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ショウジョウバエを用いたパーキンソン病の病態解明2017

    • Author(s)
      堺竜介、鈴木マリ、永井義隆
    • Journal Title

      医学のあゆみ

      Volume: 262(6) Pages: 641-646

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Studying human neurodegenerative diseases using Drosophila melanogaster2016

    • Author(s)
      鈴木マリ、永井義隆
    • Journal Title

      生体の科学

      Volume: 67 Issue: 6 Pages: 589-595

    • DOI

      10.11477/mf.2425200559

    • ISSN
      0370-9531, 1883-5503
    • Year and Date
      2016-12-15
    • Related Report
      2016 Research-status Report
  • [Journal Article] パーキンソン病リスク遺伝子GBAの機能喪失はα-シヌクレインの異常構造変化を促進して神経変性を悪化させる2016

    • Author(s)
      鈴木マリ、 藤掛伸宏、武内敏秀、香山(古金谷)綾子、中嶋和紀、平林義雄、和田圭司、永井義隆
    • Journal Title

      日本病態生理学会雑誌

      Volume: 25 Pages: 36-44

    • Related Report
      2016 Research-status Report
  • [Journal Article] Molecular Basis of Orb2 Amyloidogenesis and Blockade of Memory Consolidation2016

    • Author(s)
      Hervas R, Li L, Majumdar A, Fernandez-Ramirez Mdel C, Unruh JR, Slaughter BD, Galera-Prat A, Santana E, Suzuki M, Nagai Y, Bruix M, Casas-Tinto S, Menendez M, Laurents DV, Si K, Carrio-Vazquez M.
    • Journal Title

      PLoS Biol

      Volume: 26 Issue: 1 Pages: e1002361-e1002361

    • DOI

      10.1371/journal.pbio.1002361

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glucocerebrosidase deficiency accelerates the accumulation of proteinase K-resistant α-synuclein and aggravates neurodegeneration in a Drosophila model of Parkinson's disease.2015

    • Author(s)
      Suzuki M, Fujikake N, Takeuchi T, Kohyama-Koganeya A, Nakajima K, Hirabayashi Y, Wada K, Nagai Y.
    • Journal Title

      Hum Mol Genet. 2015 Dec 1;24(23):6675-86

      Volume: 24 Issue: 23 Pages: 6675-6686

    • DOI

      10.1093/hmg/ddv372

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Normalization of overexpressed alpha-synuclein causing Parkinson’s disease by a moderate gene silencing with RNA interference.2015

    • Author(s)
      Takahashi M., Suzuki M., Fukuoka M., Fujikake N., Watanabe S., Murata M., Wada K., Nagai Y., and *Hohjoh H.
    • Journal Title

      Mol Ther Nucleic Acids

      Volume: 4 Pages: e241-e241

    • DOI

      10.1038/mtna.2015.14

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level.2015

    • Author(s)
      Takeuchi T, Suzuki M, Fujikake N, Popiel HA, Kikuchi H, Futaki S, Wada K, Nagai Y
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: in press Issue: 19

    • DOI

      10.1073/pnas.1412651112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] GBA機能喪失はα-シヌクレインの異常構造変化を促進して神経変性を悪化させる.2017

    • Author(s)
      鈴木マリ, 藤掛伸宏, 武内敏秀, 香山(古金谷)綾子, 中嶋和紀, 平林義雄, 和田圭司, 三五一憲, 永井義隆.
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] パーキンソン病におけるαシヌクレイン-脂質相互作用の役割.2017

    • Author(s)
      鈴木マリ, 永井義隆
    • Organizer
      第12回臨床ストレス応答学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Improvement of misfolding protein-induced neurodegeneration by dietary restriction in Drosophila.2017

    • Author(s)
      Mari Suzuki, Anne-Marie Neumann, Yuji Saitoh, Nobuhiro Fujikake, Keiji Wada, Kazunori Sango, Yoshitaka Nagai.
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 食餌制限は神経変性疾患モデルショウジョウバエの神経変性を改善する.2017

    • Author(s)
      鈴木マリ, Anne-Marie Neumann, 斉藤勇二, 藤掛伸宏, 和田圭司, 三五一憲, 永井義隆.
    • Organizer
      第27回日本病態生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Dietary restriction improves neurodegeneration in Drosophila models of neurodegenerative diseases.2017

    • Author(s)
      Mari Suzuki, Anne-Marie Neumann, Yuji Saitoh, Nobuhiro Fujikake, Keiji Wada, Kazunori Sango, Yoshitaka Nagai.
    • Organizer
      EMBO/EMBL Symposium “Mechanisms of Neurodegeneration”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dietary restriction improves misfolding protein-related neurodegeneration in Drosophila.2017

    • Author(s)
      Mari Suzuki, Anne-Marie Neumann, Yuji Saitoh, Nobuhiro Fujikake, Keiji Wada, Kazunori Sango, Yoshitaka Nagai.
    • Organizer
      Keystone Symposia “Aging and Mechanisms of Aging-Related Disease”
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] グルコセレブロシダーゼ機能欠失はαシヌクレインの異常構造変化を促進して神経変性を増悪する2016

    • Author(s)
      鈴木マリ、 藤掛伸宏、武内敏秀、香山(古金谷)綾子、中嶋和紀、平林義雄、和田圭司、永井義隆
    • Organizer
      第10回 パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都ホテルオークラ(京都府京都市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] パーキンソン病リスク遺伝子GBAの機能喪失はα-シヌクレインの異常構造変化を促進して神経変性を悪化させる2016

    • Author(s)
      鈴木マリ、 藤掛伸宏、武内敏秀、香山(古金谷)綾子、中嶋和紀、平林義雄、和田圭司、永井義隆
    • Organizer
      第26回日本病態生理学会大会
    • Place of Presentation
      金沢医科大学(石川県河北郡)
    • Year and Date
      2016-08-05
    • Related Report
      2016 Research-status Report
  • [Presentation] GBA deficiency accelerates α-synuclein prion-like conversion and promotes its neurotoxicity2016

    • Author(s)
      鈴木マリ、 藤掛伸宏、武内敏秀、香山(古金谷)綾子、中嶋和紀、平林義雄、和田圭司、永井義隆
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
  • [Presentation] 神経変性疾患モデルショウジョウバエの神経変性は過栄養摂取により増悪する2015

    • Author(s)
      永井義隆、鈴木マリ、Neumann Anne-Marie、藤掛伸宏、和田圭司
    • Organizer
      第34回日本認知症学会学術集会
    • Place of Presentation
      リンクステーションホール青森(青森市堤町)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Effect of dietary conditions on Drosophila models of neurodegenerative diseases2015

    • Author(s)
      Mari Suzuki, Anne-Marie Neumann, Yuji Saitoh, Nobuhiro Fujikake, Keiji Wada, Yoshitaka Nagai
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      新潟コンベンションセンター(新潟市中央区)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Research-status Report
  • [Remarks] 糖尿病性神経障害プロジェクト

    • URL

      http://www.igakuken.or.jp/diabetic/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 国立精神・神経医療研究センタープレスリリース

    • URL

      http://www.ncnp.go.jp/press/press_release150916.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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