Fu Jian, Guo Ouyang, Zhen Zhihang, Zhen Junli
Department of Emergency Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Biology, Boston University, Boston, MA, United States.
Front Neurosci. 2020 Dec 1;14:603373. doi: 10.3389/fnins.2020.603373. eCollection 2020.
Signaling from the synapse to nucleus is mediated by the integration and propagation of both membrane potential changes (postsynaptic potentials) and intracellular second messenger cascades. The electrical propagation of postsynaptic potentials allows for rapid neural information processing, while propagating second messenger pathways link synaptic activity to the transcription of genes required for neuronal survival and adaptive changes (plasticity) underlying circuit formation and learning. The propagation of activity-induced calcium signals to the cell nucleus is a major synapse-to-nucleus communication pathway. Neuronal PAS domain protein 4 (Npas4) is a recently discovered calcium-dependent transcription factor that regulates the activation of genes involved in the homeostatic regulation of excitatory-inhibitory balance, which is critical for neural circuit formation, function, and ongoing plasticity, as well as for defense against diseases such as epilepsy. Here, we summarize recent findings on the neuroprotective functions of Npas4 and the potential of Npas4 as a therapeutic target for the treatment of acute and chronic diseases of the central nervous system.
从突触到细胞核的信号传导是由膜电位变化（突触后电位）和细胞内第二信使级联反应的整合与传播介导的。突触后电位的电传播允许快速的神经信息处理，而传播的第二信使途径将突触活动与神经元存活以及电路形成和学习基础的适应性变化（可塑性）所需基因的转录联系起来。活动诱导的钙信号向细胞核的传播是一条主要的突触到细胞核的通讯途径。神经元PAS结构域蛋白4（Npas4）是最近发现的一种钙依赖性转录因子，它调节参与兴奋性-抑制性平衡稳态调节的基因的激活，这对神经回路的形成、功能和持续可塑性以及对癫痫等疾病的防御至关重要。在这里，我们总结了关于Npas4神经保护功能的最新发现以及Npas4作为治疗中枢神经系统急性和慢性疾病治疗靶点的潜力。
