Studies in multiple experimental systems show that Ca2+-calmodulin stimulated protein kinase II (CaMKII) is a major mediator of ischaemia-induced cell death and suggest that CaMKII would be a good target for neuroprotective therapies in acute treatment of stroke. However, as CaMKII regulates many cellular processes in many tissues any clinical treatment involving the inhibition of CaMKII would need to be able to specifically target the functions of ischaemia-activated CaMKII. In this review we summarise new developments in our understanding of the molecular mechanisms involved in ischaemia-induced CaMKII-mediated cell death that have identified ways in which such specificity of CaMKII inhibition after stroke could be achieved. We also review the mechanisms and phases of tissue damage in ischaemic stroke to identify where and when CaMKII-mediated mechanisms may be involved.
Keywords: CaMKII; Excitotoxicity; Ischaemia; Neuroprotection; Protein phosphorylation; Stroke.
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