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Efficient neuronal regeneration by regulation of protease activity

Research Project

Project/Area Number 18K06708
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Kawashita Eri  京都薬科大学, 薬学部, 助教 (80509266)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsα2アンチプラスミン / 神経新生 / 移植 / 線溶 / 再生 / 線溶因子 / セルピン / α2-antiplasmin / 神経再生 / 血管新生
Outline of Final Research Achievements

α2-Antiplasmin (α2AP), a member of the serine protease inhibitor (serpin) family, is known as a principal physiological plasmin inhibitor. In this study, we demonstrated that the inhibition of α2AP by the intracerebroventricular injection of an anti-α2AP-neutralizing antibody in WT adult mice enhanced adult hippocampal neurogenesis, and the spatial memory formation and retention. We also found that α2AP is likely to be involved in endogenous neurogenesis after brain injury, and in the engraftment of ES cell-derived cortical neurons transplanted in the cerebral cortex. These findings suggest that α2AP is a potential regulator responsible for functional neurogenesis and reorganization, possibly being useful for efficient neuronal regeneration after brain injury.

Academic Significance and Societal Importance of the Research Achievements

脳梗塞や認知症、パーキンソン病など根治が困難とされてきた脳神経疾患に対して、再生医療の実現化を目指した神経細胞の移植研究が世界中で行われているが、病態の劇的な改善には、移植した神経細胞の生着性の向上が重要となる。本研究では、α2アンチプラスミン(α2AP)が、生体に本来備わっている神経再生能力や、移植細胞の生着性の向上に関与する可能性を示した。本研究成果は、効果的な神経再生療法の応用に繋がると考えている。

Report

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

    (4 results)

All 2020 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline2020

    • Author(s)
      Kawashita E, Ishihara K, Miyaji H, Tanishima Y, Kiriyama A, Matsuo O, Akiba S
    • Journal Title

      Molecular Brain

      Volume: 13 Issue: 1 Pages: 140-140

    • DOI

      10.1186/s13041-020-00677-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] α2-Antiplasmin as a regulator of adult hippocampal neurogenesis and spatial learning2020

    • Author(s)
      Eri Kawashita, Keiichi Ishihara, Osamu Matsuo, Satoshi Akiba
    • Organizer
      Gordon Research Conference: Plasminogen Activation and Extracellular Proteolysis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] α2-Antiplasmin as a potential mediator contributing to cognitive function and brain aging2018

    • Author(s)
      Eri Kawashita, Keiichi Ishihara, Yuki Enomoto, Haruko Miyaji, Osamu Matsuo, Satoshi Akiba
    • Organizer
      The 2nd Joint Meeting of the 24th International Society of Fibrinolysis and Proteolysis and the 17th Plasminogen Activation Workshop
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 記憶および脳老化へのα2-antiplasminの関与2018

    • Author(s)
      河下映里
    • Organizer
      第4回幹細胞・細胞分化に関する合同リトリート
    • Related Report
      2018 Research-status Report

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

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