NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage

2016-09-01
Kleinschnitz, Christoph
Mencl, Stine
Kleikers, Pamela W. M.
Schuhmann, Michael K.
Lopez, Manuela G.
Casas, Ana I.
Sürün, Bilge
Reif, Andreas
Schmidt, Harald H. H. W.
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.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

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Citation Formats
C. Kleinschnitz et al., “NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage,” JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, pp. 1508–1512, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/63052.