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Investigation of the relationship between autophagy and NBIA causative genes.

Research Project

Project/Area Number 15K09325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

Furuya Norihiko  順天堂大学, 医学(系)研究科(研究院), 助教 (50401188)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsオートファジー / NBIA / 鉄代謝 / フェリチン / フェリチノファジー / ミトコンドリア / 酸化ストレス / リソソーム
Outline of Final Research Achievements

Neurodegeneration with brain iron accumulation (NBIA) is a set of degenerative extrapyramidal monogenic disorders with radiological evidence of focal accumulation of iron in the brain, usually in the basal ganglia. In this study, we investigated the relationship between autophagy and NBIA causative genes. Knockdown using siRNA of a part of NBIA genes influenced autophagy or lysosomal system. To investigate those genes function more precisely, we tried to establish knockout (KO) cell lines using CRISPR/Cas9 system. We could successfully obtain FTL KO cells. FTL KO cells showed the reduction of ferritin-selective autophagy (ferritinophagy) flux, the reduction of mitochondrial function and the vulnerability against oxidative stress. Those phenotypes of FTL KO cells must tightly associate with the mechanism of NBIA disease onset.

Report

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

    (8 results)

All 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (2 results) Book (3 results)

  • [Journal Article] Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson's disease.2017

    • Author(s)
      Saiki S, Hatano T, Fujimaki M, Ishikawa K, Mori A, Oji Y, Okuzumi A, Fukuhara T, Koinuma T, Nagumo M, Furuya N, Nojiri S, Amo T, Yamashiro K, Hattori N.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 7328-7328

    • DOI

      10.1038/s41598-017-06767-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] VPS29-VPS35 intermediate of retromer is stable and may be involved in the retromer complex assembly process.2015

    • Author(s)
      Fuse A, Furuya N, Kakuta S, Inose A, Sato M, Koike M, Saiki S, Hattori N
    • Journal Title

      FEBS Lett.

      Volume: 589 Issue: 13 Pages: 1430-1436

    • DOI

      10.1016/j.febslet.2015.04.040

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation.2015

    • Author(s)
      Yamada D, Saiki S, Furuya N, Ishikawa K, Imamichi Y, Kambe T, Fujimura T, Ueno T, Koike M, Sumiyoshi K, Hattori N
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 471 Issue: 1 Pages: 109-116

    • DOI

      10.1016/j.bbrc.2016.01.171

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] NDP52を介したマイトファゴソーム形成機構の解析2016

    • Author(s)
      古屋徳彦
    • Organizer
      第4回新学術「オートファジー」班会議、第10回オートファジー研究会
    • Place of Presentation
      新潟県南魚沼郡湯沢町
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
  • [Presentation] マイトファジーにおけるNDP52-LC3C経路の解析2015

    • Author(s)
      古屋徳彦
    • Organizer
      第9回オートファジー研究会・第3回「オートファジー」班会議
    • Place of Presentation
      兵庫県淡路市
    • Year and Date
      2015-11-16
    • Related Report
      2015 Research-status Report
  • [Book] Methods Mol Biol.2017

    • Author(s)
      Furuya N
    • Publisher
      Springer
    • Related Report
      2017 Annual Research Report
  • [Book] Methods Mol Biol.2017

    • Author(s)
      Sato S, Furuya N.
    • Publisher
      Springer
    • Related Report
      2017 Annual Research Report
  • [Book] Methods in Molecular Biology "Induction of PINK1/Parkin-Mediated Mitophagy"2017

    • Author(s)
      Sato S, Furuya N
    • Total Pages
      9
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report

URL: 

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

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