| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MG6(RCB2403) |
