NOS knockout or inhibition but not disrupting PSD 95 NOS interaction protect against ischemic brain damage
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 in vivo and in vitro, but find three pharmacological post synaptic density protein 95 inhibitors to be therapeutically ineffective.
Journal of cerebral blood flow and metabolism official journal of the International Society of Cerebral Blood Flow and Metabolism