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The exploration of pathophysiology and therapeutic development of PD by targeting exosomes

Research Project

Project/Area Number 16H07185
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionJuntendo University

Principal Investigator

Tsunemi Taiji  順天堂大学, 医学(系)研究科(研究院), 准教授 (50401344)

Project Period (FY) 2016-08-26 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsパーキンソン病 / Kufor-Rakeb症候群 / アルファシヌクレイン / エキソソーム / ATP13A2 / PARK9 / 遺伝学 / 神経科学 / 脳神経疾患 / 細胞・組織 / トランスレーショナルリサーチ / iPS細胞 / ドーパミン細胞 / ライソゾーム / αシヌクレイン / FYVEタンパク質 / ALIX / 脳・神経
Outline of Final Research Achievements

By screening FYVE proteins through in vitro invagination assay, “Protein A”, which is associated with ATP13A2/PARK9 was discovered. It is co-localized with ATP13A2 on endosomes, and the association of two proteins was determined by immunoprecipitation analysis. The localization of Protein A is altered in ATP13A2-deficient cells. The functional association between two proteins is under investigation.

At the early stage after the initiation of differentiation of dopaminergic neurons taken from patients with Kufor-Rakeb syndrome, the secretion of exosomes was already reduced. Lentiviral shRNA against ALIX enhanced the secretion of exosomes and attenuated alpha synuclein accumulation and abnormal mitochondrial respiration, suggesting that the main pathology of KRS involves the impaired exosome secretion, and therefore, improving this pathway would be beneficial to the issues observed in other intracellular organelles.

Report

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

    (10 results)

All 2018 2017 2016

All Journal Article (4 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] 総論 特集“脊髄小脳変性症の最近の治療と研究”2018

    • Author(s)
      常深泰司、服部信孝
    • Journal Title

      難病と在宅ケア

      Volume: 23 Pages: 5-8

    • NAID

      40021455260

    • Related Report
      2017 Annual Research Report
  • [Journal Article] パーキンソン症状をきたす脊髄小脳変性症2018

    • Author(s)
      石黒雄太、常深泰司、服部信孝
    • Journal Title

      難病と在宅ケア

      Volume: 23 Pages: 17-20

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 日本におけるパーキンソン病治療の変遷と展望2017

    • Author(s)
      常深泰司、服部信孝
    • Journal Title

      日本臨床

      Volume: 75 Pages: 14-20

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 日本におけるパーキンソン病治療の変遷と展望 特集 パーキンソン病2017

    • Author(s)
      常深泰司、服部信孝
    • Journal Title

      日本臨床

      Volume: 75 Pages: 14-20

    • Related Report
      2016 Annual Research Report
  • [Presentation] ATP13A2/PARK9 regulates intracellular a-synuclein levels through exocytotic pathways2017

    • Author(s)
      Taiji Tsunemi, Yuta Ishiguro, Katarina Trajkovic, Zong Xie, Tamara Perez-Rosello, Joseph Mazzulli, Wado Akamatsu, Haoxing Xu, Jim Surmeier, Dimitri Krainc, Nobutaka Hattori
    • Organizer
      WCN2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ATP13A2/PARK9 deficiency leads to impaired lysosomal exocytosis2017

    • Author(s)
      Taiji Tsunemi, Asako Yoroizaka, Wado Akamatsu, Hattori Nobutaka
    • Organizer
      老人性疾患病態・治療研究センター / ゲノム・再生医療センター 合同研究発表会
    • Place of Presentation
      東京 順天堂大学
    • Related Report
      2016 Annual Research Report
  • [Presentation] エキソソームをターゲットとしたパーキンソン病の病態解明と新規治療法の開発2016

    • Author(s)
      Taiji Tsunemi, Clarissa Valdez, Katarina Trajkovic, Asako Yoroizaka, Kana Hamada, Sohee Jeon, Malini Krishna Vangipurum Suresh, Nobutaka Hattori, Dimitri Krainc
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Kufor-Rakeb症候群の病態から考えるパーキンソン病の発症機序2016

    • Author(s)
      常深泰司
    • Organizer
      御茶ノ水神経内科懇話会
    • Place of Presentation
      東京 ホテルモントレ半蔵門
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Kufor-Rakeb症候群におけるエンドライソゾーム機能障害2016

    • Author(s)
      常深泰司
    • Organizer
      第35回日本認知症学会
    • Place of Presentation
      東京フォーラム
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] ブレインサイエンスレヴュー20182018

    • Author(s)
      常深泰司
    • Publisher
      ブレインサイエンス振興財団
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-09-02   Modified: 2019-03-29  

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