A Novel Therapeutic Peptide as a Partial Agonist of RANKL in Ischemic Stroke

作者：Kurinami Hitomi; Shimamura Munehisa^*; Nakagami Hironori; Shimizu Hideo; Koriyama Hiroshi; Kawano Tomohiro; Wakayama Kouji; Mochizuki Hideki; Rakugi Hiromi; Morishita Ryuichi^*

来源：Scientific Reports, 2016, 6(1): 38062.

DOI：10.1038/srep38062

The enhanced receptor activator of nuclear factor-kappa B (NF kappa B) ligand (RANKL) and its receptor (RANK) signal have been reported to attenuate ischemic brain injury through inhibition of Toll-like receptor (TLR) 4-mediated inflammation. However, augmentation of the RANKL/RANK signal also accelerates osteoporosis, which is a potential problem in clinical use of RANKL. Therefore, we developed novel peptides, microglial healing peptides (MHPs), which were based on the DE and/or EF loop of RANKL. Among them, MHP1 was the most effective inhibitor of TLR4-induced inflammations in microglia/macrophages. The effects depended on RANK, as confirmed by knockdown experiments. In contrast to RANKL, MHP1 did not stimulate osteoclast differentiation. Unexpectedly, MHP1 inhibited RANKL-induced osteoclast differentiation. These findings suggested that MHP1 was a partial agonist of RANKL, and administration of MHP1 attenuated ischemic injury by decreasing inflammation. MHP1 could be a novel therapeutic agent for treating ischemic stroke.

• 出版日期2016-11-29