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The study about the mechanism underlying brain iron accumulation in the deficiency of iPLA2 beta.

Research Project

Project/Area Number 24591294
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

BECK Goichi  大阪大学, 医学部附属病院, 医員 (20626353)

Co-Investigator(Kenkyū-buntansha) SUMI Hisae  大阪大学, 医学系研究科, 助教 (30403059)
MOCHIZUKI Hideki  大阪大学, 医学系研究科, 教授 (90230044)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsNBIA2 / PLA2G6 / DMT1 / 鉄調節蛋白質 / ミトコンドリア / NBIA / IRP / 神経筋疾患 / 神経病理 / カルシウム非依存性フォスフォリパーゼA2β / SH-SY5Y細胞
Outline of Final Research Achievements

Mutations in PLA2G6 (iPLA2 beta) have been proposed to be the cause of neurodegeneration with brain iron accumulation type 2. The present study aimed to clarify the mechanism underlying brain iron accumulation during the deficiency of iPLA2 beta. We demonstrated that marked iron deposition was observed in the brains of PLA2G6-KO mice since the early clinical stages. Divalent metal transporter 1 (DMT1) and iron regulatory proteins (IRPs) were markedly upregulated in the brains of aged PLA2G6-KO mice compared to age-matched wild-type control mice. DMT1 and IRPs were significantly upregulated in PLA2G6-KD cells. Degeneration of the mitochondrial inner membrane and decrease of ATP production were observed in PLA2G6-KD cells. These results suggest that the genetic ablation of iPLA2 beta increased iron uptake in the brain through the activation of IRPs and upregulation of DMT1, which was induced by mitochondrial dysfunction.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013 Other

All Journal Article (2 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Invited: 2 results)

  • [Journal Article] Neuroaxonal dystrophy in PLA2G6 knockout mice2015

    • Author(s)
      Sumi H, Beck G, Kato S, Mochizuki H
    • Journal Title

      Neuropathology

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PLA2G6(PARK14)遺伝子欠損に伴う軸索変性の病態2013

    • Author(s)
      隅寿恵, 別宮豪一, 望月秀樹
    • Journal Title

      医学のあゆみ

      Volume: 247 Pages: 1061-1068

    • Related Report
      2013 Research-status Report
  • [Presentation] Loss of calcium-independent phospholipase A2β causes degeneration of mitochondrial and presynaptic membranes in neurons2015

    • Author(s)
      Goichi Beck, Hisae Sumi-Akamaru, Koei Shinzawa, Yuki Sugiura, Mitsutoshi Setou, Yoshihide Tsujimoto, and Hideki Mochizuki
    • Organizer
      6th international conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-02-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Neuroaxonal dystrophy in PLA2G6 gene knockout mice2014

    • Author(s)
      Hisae Sumi-Akamaru, Goichi Beck, Hideki Mochizuki
    • Organizer
      第55回日本神経病理学会総会学術研究会
    • Place of Presentation
      Tokyo
    • Year and Date
      2014-06-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Neuroaxonal dystrophy in the striatum of PLA2G6 knockout mice2014

    • Author(s)
      隅寿恵、別宮豪一、伊藤朝子、新沢康英、加藤信介、辻本賀英、佐古田三郎、望月秀樹
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] PLA2G6遺伝子ノックダウンによるαシヌクレインの細胞内動態2014

    • Author(s)
      別宮豪一、隅寿恵、新沢康英、早川英規、辻本賀英、望月秀樹
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] PLA2G6(Park14)遺伝子欠損マウスにおける神経変性のメカニズム2014

    • Author(s)
      望月秀樹、隅寿恵、別宮豪一、新沢康英、辻本賀英
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Brain iron accumulation in calcium-independent phospholipase A2 beta knockout mice

    • Author(s)
      Goichi Beck, Hisae Sumi-Akamaru, Koei Shinzawa, Toru Yasuda, Yoshihide Tsujimoto, Hideki Mochizuki
    • Organizer
      Twenty-third Meeting of the European Neurological Society
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2013 Research-status Report
  • [Presentation] PLA2G6遺伝子欠損マウス脊髄神経細胞における異常ミトコンドリアとユビキチン陽性の変性軸索の関係

    • Author(s)
      隅寿恵、別宮豪一、新沢康英、加藤信介、佐古田三郎、辻本賀英、望月秀樹
    • Organizer
      第54回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] PLA2G6遺伝子欠損マウス脳におけるtyrosine hydroxylase陽性異常構造物の経時的変化

    • Author(s)
      別宮豪一、隅寿恵、新沢康英、安田徹、辻本賀英、佐古田三郎、望月秀樹
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] PLA2G6遺伝子欠損マウス脊髄におけるユビキチン陽性構造物と軸索変性

    • Author(s)
      隅寿恵、別宮豪一、新沢康英、加藤信介、佐古田三郎、辻本賀英、望月秀樹
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] PLA2G6遺伝子欠損マウス線条体におけるドパミン神経終末マーカーの変化

    • Author(s)
      隅寿恵、別宮豪一、新沢康英、早川英規、辻本賀英、望月秀樹
    • Organizer
      第7回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] iPLA2β遺伝子欠損マウス脳における鉄沈着および軸索変性との関連性の検討

    • Author(s)
      白井 良樹、別宮 豪一、隅 寿恵、新沢 康英、安田 徹、辻本 賀英、望月 秀樹
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] PLA2G6遺伝子欠損マウス脊髄におけるリン酸化αシヌクレインの蓄積

    • Author(s)
      隅 寿恵、別宮 豪一、加藤 信介、新沢 康英、安田 徹、辻本 賀英、佐古田 三郎、望月 秀樹
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] iPLA2β遺伝子欠損マウス脳における鉄沈着および軸索変性との関連性の検討

    • Author(s)
      別宮 豪一、隅 寿恵、白井 良樹、安田 徹、新沢 康英、辻本 賀英、望月 秀樹
    • Organizer
      第53回日本神経病理学会総会学術研究会
    • Place of Presentation
      新潟
    • Related Report
      2012 Research-status Report
  • [Presentation] 筋委縮性側索硬化症の脊髄白質におけるリン酸化TDP-43の局在

    • Author(s)
      隅 寿恵、別宮 豪一、加藤 信介、山寺 みさき、藤村 晴俊、望月 秀樹
    • Organizer
      第53回日本神経病理学会総会学術研究会
    • Place of Presentation
      新潟
    • Related Report
      2012 Research-status Report
  • [Presentation] PLA2G6遺伝子欠損マウスにおけるドパミン作動性神経系の変性

    • Author(s)
      別宮 豪一、隅 寿恵、新沢 康英、加藤 信介、安田 徹、辻本 賀英、望月 秀樹
    • Organizer
      第6回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] PLA2G6遺伝子欠損マウスにおけるリン酸化αシヌクレインの神経細胞内蓄積と軸索内輸送

    • Author(s)
      隅 寿恵、別宮 豪一、新沢 康英、加藤 信介、安田 徹、辻本 賀英、佐古田 三郎、望月 秀樹
    • Organizer
      第6回パーキンソン病・運動障害疾患コングレス
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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