Calmodulin Kinase IV–dependent CREB activation is required for neuroprotection via NMDA receptor‐PSD95 disruption

This study highlights the importance of maintaining neuronal function following ischaemic injury. Future stroke research should target neurotrophic and pro‐survival signal pathways in the development of novel neuroprotective strategies. 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.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fjnc.12176

Source: Journal of Neurochemistry - March 3, 2013 Category: Neurology Authors: Karen F. S. Bell, Russell J. Bent, Saira Meese‐Tamuri, Alicia Ali, Joan P. Forder, Michelle M. Aarts Tags: Original Article Source Type: research