Rostas John A P, Spratt Neil J, Dickson Phillip W, Skelding Kathryn A
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan NSW 2308, Australia; Hunter Medical Research Institute, Lot 1, Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia.
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan NSW 2308, Australia; Hunter Medical Research Institute, Lot 1, Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia.
Neurochem Int. 2017 Jul;107:33-42. doi: 10.1016/j.neuint.2017.01.012. Epub 2017 Jan 31.
Studies in multiple experimental systems show that Ca-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.
在多个实验系统中进行的研究表明，钙 - 钙调蛋白依赖性蛋白激酶II（CaMKII）是缺血诱导的细胞死亡的主要介导因子，并表明CaMKII将是急性中风神经保护治疗的一个良好靶点。然而，由于CaMKII调节许多组织中的许多细胞过程，任何涉及抑制CaMKII的临床治疗都需要能够特异性地靶向缺血激活的CaMKII的功能。在这篇综述中，我们总结了我们对缺血诱导的CaMKII介导的细胞死亡所涉及的分子机制的理解的新进展，这些进展已经确定了中风后实现CaMKII抑制特异性的方法。我们还综述了缺血性中风中组织损伤的机制和阶段，以确定CaMKII介导的机制可能在何处以及何时起作用。
