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：

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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。


鉴于肽对蛋白质-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。本研究探讨PDZ1抑制肽对缺血神经元凋亡的影响及其机制。结果表明，PDZ1 抑制剂肽可显着破坏 GluK2-PSD-95 相互作用，有效保护神经元免受缺血/再灌注诱导的细胞凋亡。此外，在全脑缺血后，PDZ1 抑制 FasL 表达、DISC 组装以及 Caspase 8、Bid、Caspase 9 和 Caspase 3 的激活。基于我们之前报道的GluK2-PSD-95通路在全脑缺血后增加FasL表达，认为PDZ1抑制肽的神经元保护作用是通过破坏GluK2-PSD-95相互作用并随后抑制FasL表达和Fas凋亡通路来实现的。