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Development of a novel treatment for Parkinson's disease focusing on the protective effect of CSPa phosphorylation on synaptic terminal

Research Project

Project/Area Number 18K06700
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionKobe University

Principal Investigator

Shirafuji Toshihiko  神戸大学, 医学研究科, 特命助教 (30595765)

Co-Investigator(Kenkyū-buntansha) 齋藤 尚亮  神戸大学, バイオシグナル総合研究センター, 名誉教授 (60178499)
上山 健彦  神戸大学, バイオシグナル総合研究センター, 教授 (80346254)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsパーキンソン病 / PKC / リン酸化 / CSPa / アデノ随伴ウイルス / プレシナプス / AAV / HSP70 / シャペロン / CSPalpha / リン酸化抗体 / CSP alpha
Outline of Final Research Achievements

I generated antibodies against Ser34 phosphorylation of CSPa (CSPa pS34 antibody) and confirmed that CSPa pS34 antibody can indeed specifically identify Ser34 phosphorylation. In CSPa extracted from whole mouse brain, the CSPa pS34 antibody detected a band. On the other hand, this antibody did not work in immunohistochemistry. Four AAV PHP.eB were generated under the control of rTHp promoter: CSPa-WT, phosphorylation-deficient (SA), phosphorylation-mimicking (SD), and H43Q. We confirmed their expression in the substantia nigra striatum by administration via the orbital venous plexus. The ratio of expression to that of endogenous CSPa is currently being verified.

Academic Significance and Societal Importance of the Research Achievements

高齢社会を迎え、加齢とともに発症するパーキンソン病などの神経変性疾患の治療法を確立することは喫緊の課題である。パーキンソン病はドパミン神経終末の変性に引き続き、ドパミン神経死を起こす病気である。シナプス小胞に局在するシャペロンのa-synucleinの機能不全が発症に関与するが、病態は未解明で、細胞死を防ぐ方法は確立していない。本研究ではCSPaのリン酸化に着目してパーキンソン病を治療しようとするものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Spinocerebellar ataxia type 14 caused by a nonsense mutation in the PRKCG gene2019

    • Author(s)
      Shirafuji Toshihiko、Shimazaki Haruo、Miyagi Tatsuhiro、Ueyama Takehiko、Adachi Naoko、Tanaka Shigeru、Hide Izumi、Saito Naoaki、Sakai Norio
    • Journal Title

      Molecular and Cellular Neuroscience

      Volume: 98 Pages: 46-53

    • DOI

      10.1016/j.mcn.2019.05.005

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cysteine String Protein alpha (CSPa)Ser34特異的リン酸化抗体の作製と機能解析2019

    • Author(s)
      白藤俊彦, 上山健彦, 足立直子, 齋藤尚亮
    • Organizer
      第60回日本組織細胞化学会総会
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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