Karen F. S. Bell, Russell J. Bent, Saira Meese-Tamuri, Alicia Ali, Joan P. Forder and Michelle M. Aarts Calmodulin Kinase IV–dependent CREB activation is required for neuroprotection via NMDA receptor-PSD95 disruption Journal of Neurochemistry 126
We propose that uncoupling NMDA receptors from PSD95 provides neuroprotection from stroke by enhancing Ca2+/Calmodulin-dependent neurotrophic signalling. Blocking NMDAR-PSD95 interactions allows enhanced activation of nuclear CaM-kinase IV and prolonged phosphorylation of the CREB transcription factor, resulting in enhanced neurotrophic transcription. These findings demonstrate the importance of maintaining neurotrophic, Ca2 + -dependent signalling during neuronal injury and provide novel targets for neuroprotection in stroke.
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