Ca 2+/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) is a member of a family of Ca 2+/calmodulin-regulated protein kinases which also includes Ca 2+/calmodulin-dependent protein kinases Ⅰ and Ⅲ, myosin light chain kinases and phosphorylase kinase. Unlike the other members of this family, CaMKⅡ is multifunctional protein kinase and distributes in a variety of tissues. It is especially abundant in neuronal system. In hippocampus, CaMKⅡ is about 2% of the total protein. Studies have shown that CaMKⅡ plays an important role in a variety of biological processes, such as regulation of gene transcription, synthesis of neurotransmitter, phosphorylation of cytoskeletonal protein, hippocampal learning and memory formation.
Alzheimer病(AD)中,异常过度磷酸化的tau蛋白会导致细胞骨架的异常并与神经元的死亡有关.在体外,细胞周期蛋白依赖性蛋白激酶5(cdk-5)能在大多数AD相关位点磷酸化tau蛋白.旨在整体水平研究cdk-5过度表达对大鼠微管相关蛋白tau的磷酸化及空间记忆的影响.结果显示,在大鼠海马区转染 cdk-5基因,24h后其局部表达增加,并使得抗体tau-1显色减弱,PHF-1和12e8显色增强,提示tau蛋白在Ser199/202,Ser396/404和Ser262/356位点过度磷酸化.此外,在水迷宫测试中,cdk-5转染鼠寻找安全平台所需时间比对照鼠明显延长,而转染后48 h cdk-5的表达较 24h时下降,同时伴有tau蛋白磷酸化程度的下降和空间记忆能力的改善.这些结果提示整体水平的cdk-5的过度表达会导致大鼠的空间记忆损伤,而过度磷酸化的tau蛋白可能参与了该病理过程.
