論文 - 詳細
| RRC ID | 56075 |
|---|---|
| 著者 | Shimamura M, Nakagami H, Shimizu H, Mukai H, Watanabe R, Okuzono T, Kawano T, Ikeda Y, Hayashi H, Yoshida S, Ju N, Mochizuki H, Morishita R. |
| タイトル | Development of a novel RANKL-based peptide, microglial healing peptide1-AcN (MHP1-AcN), for treatment of ischemic stroke. |
| ジャーナル | Sci Rep |
| Abstract |
Although the regulation of post-ischemic inflammation is an important strategy to treat ischemic stroke, all clinical trials have failed to show its efficacy. To solve the problem, we previously developed a novel partial peptide of RANKL, microglial healing peptide 1 (MHP1), which could reduce ischemic injury by inhibiting Toll-like receptor (TLR) induced inflammation. However, optimization of the peptide was necessary to increase the stability and efficacies for clinical use. According to information gathered through HPLC/MS in serum, we have newly designed a series of modified MHP1 peptides and have found that N-terminal acetylation and C-terminal amidation in MHP1 (MHP1-AcN), can strengthen its anti-inflammatory effects and increase its stability with anti-osteoclastogenic effects. Anti-TLR activity was reported to be reduced in MHP1 when incubated at 37 °C for 24 hrs, but MHP1-AcN could keep the activity under the same condition. The therapeutic effect of MHP1-AcN was observed in transient ischemic stroke model at lower dose than MHP1. Importantly, MHP1-AcN did not affect thrombolytic effects of tissue plasminogen activator (tPA) and inhibited tPA-induced hemorrhagic transformation. These findings indicated that MHP1-AcN was stable and effective anti-TLR signal peptide and could be a promising agent for treating stroke patients receiving tPA and endovascular therapy. |
| 巻・号 | 8(1) |
| ページ | 17770 |
| 公開日 | 2018-12-11 |
| DOI | 10.1038/s41598-018-35898-z |
| PII | 10.1038/s41598-018-35898-z |
| PMID | 30538259 |
| PMC | PMC6290023 |
| MeSH | Amino Acid Sequence Animals Brain Ischemia / drug therapy* Fibrinolytic Agents / therapeutic use Male Mice Mice, Inbred ICR Microglia / physiology Peptides / therapeutic use RANK Ligand / therapeutic use* Stroke / therapy* Tissue Plasminogen Activator / administration & dosage |
| IF | 4.011 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MG6(RCB2403) |