Respecting the selective inhibition of peptides on protein-protein interactions, they might become potent methods in ischemic stroke therapy. In this study, we investigated the effect of PDZ1 inhibitor peptide on ischemic neuron apoptosis and the relative mechanism. Results showed that PDZ1 inhibitor peptide, which significantly disrupted GluK2-PSD-95 interaction, efficiently protected neuron from ischemia/reperfusion-induced apoptosis. Further, PDZ1 inhibited FasL expression, DISC assembly and activation of Caspase 8, Bid, Caspase 9 and Caspase 3 after global brain ischemia. Based on our previous report that GluK2-PSD-95 pathway increased FasL expression after global brain ischemia, the neuron protection effect of PDZ1 inhibitor peptide was considered to be achieved by disrupting GluK2-PSD-95 interaction and subsequently inhibiting FasL expression and Fas apoptosis pathway.

中文翻译：

---

PDZ1抑制剂肽通过抑制GluK2-PSD-95-模块介导的Fas信号通路来保护神经元免受缺血。

考虑到肽对蛋白质-蛋白质相互作用的选择性抑制，它们可能成为缺血性中风治疗的有效方法。在这项研究中，我们研究了PDZ1抑制剂肽对缺血性神经元凋亡的影响及其相关机制。结果表明，PDZ1抑制剂肽可显着破坏GluK2-PSD-95的相互作用，可有效保护神经元免受缺血/再灌注诱导的细胞凋亡。此外，PDZ1抑制了全脑缺血后FasL的表达，DISC的组装以及Caspase 8，Bid，Caspase 9和Caspase 3的激活。根据我们先前的报道，全球脑缺血后GluK2-PSD-95途径增加FasL表达，