NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage
NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage
复制标题
DOI：
10.1177/0271678x16657094
复制
发表时间：
2016-09-01
影响因子：
6.3
通讯作者：
Schmidt, Harald H. H. W.
中科院分区：
文献类型：
--
作者：
Kleinschnitz, Christoph;Mencl, Stine;Schmidt, Harald H. H. W.
据报道，临床前卒中靶点验证的药理学原理破坏了N-甲基-D-天冬氨酸受体-突触后密度蛋白-95-神经元型一氧化氮合酶复合体，取得了可喜的结果。然而，突触后密度蛋白-95也与潜在的神经保护机制相耦合。由于突触后密度蛋白-95抑制剂可能干扰潜在的神经保护机制，并且充分的验证通常是翻译基础中风研究的一个问题，我们希望通过比较突触后密度蛋白-95抑制剂与NOS1(-/-)小鼠和NOS抑制剂来缩小这一差距。我们在体内和体外都证实了NOS1在中风中的有害作用，但发现三种药物突触后密度蛋白-95抑制剂在治疗上无效。
Promising results have been reported in preclinical stroke target validation for pharmacological principles that disrupt the N-methyl-D-aspartate receptor-post-synaptic density protein-95-neuronal nitric oxide synthase complex. However, post-synaptic density protein-95 is also coupled to potentially neuroprotective mechanisms. As post-synaptic density protein-95 inhibitors may interfere with potentially neuroprotective mechanisms and sufficient validation has often been an issue in translating basic stroke research, we wanted to close that gap by comparing post-synaptic density protein-95 inhibitors with NOS1(-/-) mice and a NOS inhibitor. We confirm the deleterious role of NOS1 in stroke both invivo and invitro, but find three pharmacological post-synaptic density protein-95 inhibitors to be therapeutically ineffective.