已确认黏膜相关淋巴样组织淋巴瘤转座蛋白1（MALT1）通过促进兴奋性毒性和坏死样凋亡，在缺血性脑卒中中贡献于脑损伤。预测抗丙型肝炎病毒蛋白酶抑制剂Telaprevir可能是一个潜在的MALT1抑制剂。在这里，我们证明了Telaprevir通过抑制MALT1来保护脑缺血性损伤，从而防止谷氨酸受体离子型NMDA 2B（GluN2B）活化，限制钙过载和抑制坏死样凋亡。在缺血性脑卒中小鼠中，Telaprevir减少了梗死体积，改善了长期存活率，并增强了感觉运动、记忆和认知功能。在缺氧处理的神经细胞中，Telaprevir降低了细胞内钙浓度，减少了LDH的释放。从机制上看，Telaprevir抑制了MALT1蛋白酶活性，从而通过降低STEP61的水平，降低了GluN2B膜蛋白水平和磷酸化。此外，Telaprevir能够抑制坏死样凋亡相关蛋白的水平。根据这些结果，可以得出结论Telaprevir通过限制GluN2B活化和抑制MALT1来减轻中风小鼠的神经脑损伤，从而抑制了受体相互作用蛋白激酶1（RIPK1）/受体相互作用蛋白激酶3（RIPK3）/混合家族激酶结构域伪激酶（MLKL）途径。因此，Telaprevir可能具有治疗缺血性脑卒中患者的新型适应症。

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has been confirmed to contribute to brain injury in ischemic stroke via promoting excitotoxicity and necroptosis. Telaprevir, a hepatitis C virus protease inhibitor, is predicted to be a potential MALT1 inhibitor. Here, we showed that telaprevir protected against cerebral ischemic injury via inhibiting MALT1, thereby preventing glutamate receptor ionotropic NMDA 2B (GluN2B) activation, limiting calcium overload, and suppressing necroptosis. In ischemic stroke mice, telaprevir reduced infarct volume, improved the long-term survival rate, and enhanced sensorimotor, memory, and cognitive functions. In hypoxia-treated nerve cells, telaprevir decreased the intracellular calcium concentrations and reduced LDH release. Mechanistically, telaprevir inhibited MALT1 protease activity, thus decreasing the membrane protein level of GluN2B and its phosphorylation through reducing the level of STEP61. Moreover, telaprevir was able to inhibit the levels of necroptosis-associated proteins. According to these results, it can be concluded that telaprevir alleviates neuronal brain injury in stroke mice via restraining GluN2B activation and suppresses the receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway through inhibiting MALT1. Thus, telaprevir might have a novel indication for treating patients with ischemic stroke.