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Development of a novel anti-inflammatory peptide targetting RANK signal in ischemic stroke

Research Project

Project/Area Number 15K10300
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Kurinami Hitomi  大阪大学, 医学部附属病院, 助教 (10638555)

Co-Investigator(Kenkyū-buntansha) 島村 宗尚  大阪大学, 医学系研究科, 寄附講座准教授 (60422317)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords炎症 / 脳梗塞 / RANKL / RANK / 合成ペプチド / Toll-like receptor / マクロファージ / ミクログリア / RANKLペプチド
Outline of Final Research Achievements

MHP1 is a newly developed synthetic peptide composed of the DE and a part of the EF loop of the receptor activator of nuclear factor-кB (NFκB) ligand (RANKL). In this study, we demonstrated that MHP1 significantly inhibits Toll-like receptor (TLR) 2-, 4-, and 7/8- induced inflammation in microglia/macrophages without osteoclast activation. Knockdown of RANK receptor cancelled the anti-inflammatory effects, indicating that the effects were through RANK signal. HPLC/MS analysis showed that around 50% of MHP1 still remained after 30 minutes; in fact, the active sites of MHP1 were still preserved in some of the degradation products. In mice with tMCAo, MHP1 could cross the blood-brain-barrier in peri-infarct regions. The administration of MHP1 4 or 6 hours after cerebral ischemia successfully reduced infarct volume and prevented the exacerbation of neurological deficits without affecting osteoclast activation. MHP1 peptide could be a novel agent for the treatment ischemic stroke.

Report

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

Research Products

(5 results)

All 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] A Novel Therapeutic Peptide as a Partial Agonist of RANKL in Ischemic Stroke2016

    • Author(s)
      Kurinami H, Shimamura M, Nakagami H, Shimizu H, Koriyama H, Kawano T, Wakayama K, Mochizuki H, Rakugi H, Morishita R
    • Journal Title

      Sci Rep

      Volume: 29

    • DOI

      10.1038/srep38062

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Development of a novel anti-inflammatory and anti-osteoplastic peptide based on DE-loop and EF-loop in RANKL for treatment of ischemic stroke2016

    • Author(s)
      Hitomi Kurinami
    • Organizer
      International Stroke Conference 2016
    • Place of Presentation
      Los Angels(アメリカ)
    • Year and Date
      2016-02-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel partial anosit-like RANKL peptide inhibiting TLR-induced inflammation in ischemic brain2016

    • Author(s)
      島村宗尚
    • Organizer
      日本神経学会
    • Place of Presentation
      兵庫
    • Related Report
      2016 Research-status Report
  • [Presentation] Development of a novel anti-inflammatory and anti-osteoclastic peptide based on rankl for treatment of ischemic stroke.2016

    • Author(s)
      Hitomi Kurinami
    • Organizer
      Society for Neuroscience 2016
    • Place of Presentation
      米国
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 炎症性サイトカイン分泌抑制活性を有するオリゴペプチド2015

    • Inventor(s)
      栗波仁美、島村宗尚 他
    • Industrial Property Rights Holder
      栗波仁美、島村宗尚 他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-102502
    • Filing Date
      2015-05-20
    • Related Report
      2015 Research-status Report

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

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