Abstract—Regulation of adaptive mechanisms in the central nervous system in cerebrovascular disorders and during the development of pathological processes is an urgent problems in neurobiology and medicine. Kinases, enzymes that perform a wide range of functions in the central nervous system, are of great interest as molecular targets and possible therapeutic agents in various neurodegenerative processes and impaired energy metabolism in the nervous tissue. The vast majority of intracellular reactions that lead to activation of neuroprotective mechanisms or, conversely, cell death reactions are associated with kinase activity. Nevertheless, the functioning of kinases in pathological processes in the central nervous system is poorly understood. Here, we identified components of the neuronal kinome with previously undescribed neuroprotective properties. We evaluated cell viability and characterized the morphology of primary brain cell cultures after treatment with 34 kinase inhibitors under conditions of modeled stress (glucose deprivation). We identified several groups of neuronal kinome with different actions and characterized the most physiologically relevant kinases. It was shown that blockage of eEF2K, SRC, and IKKb (IKK2) kinases, and the structurally close associated group of kinases JAK2, CDK2/CyclinA, CDK2/CyclinE, and FLT3 maintain cell viability in primary neuronal cultures during glucose deprivation in vitro. For the several most functionally important kinases, we estimated their influence on functional calcium activity of primary neuronal cultures. The data revealed that blockage of IKKb and eEF2K kinases effectively preserves the viability of neuronal cells under glucose deprivation but does not maintain the functional calcium activity of neuron-glial networks.

摘要-在脑血管疾病和病理过程发展过程中调节中枢神经系统的适应性机制是神经生物学和医学中的迫切问题。激酶是在中枢神经系统中执行多种功能的酶，作为分子靶标和各种神经退行性过程以及神经组织能量代谢受损的可能治疗剂引起了人们的极大兴趣。导致神经保护机制激活的绝大多数细胞内反应，或者相反地，细胞死亡反应与激酶活性有关。然而，人们对中枢神经系统病理过程中激酶的功能了解甚少。在这里，我们确定了具有先前未描述的神经保护特性的神经元动能组。我们评估了细胞生存能力，并在模拟应激（葡萄糖剥夺）条件下用34种激酶抑制剂处理后表征了原代脑细胞培养的形态。我们确定了几组具有不同作用的神经元激酶组，并表征了最生理相关的激酶。研究表明，eEF2K，SRC和IKKb（IKK2）激酶以及激酶JAK2，CDK2 / CyclinA，CDK2 / CyclinE和FLT3的结构紧密相关的基团在体外葡萄糖剥夺过程中均能维持细胞活力。对于几种功能最重要的激酶，我们估计了它们对原代神经元培养物的功能钙活性的影响。