Development of a novel anti-inflammatory peptide targetting RANK signal in ischemic stroke
| Project/Area Number |
15K10300
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(5 results)
