Abstract—NF-κB is a family of nuclear transcription factors that play a leading role in the pathogenesis of many chronic inflammatory processes and in immune response regulation. At the end of the last century, NF-κB was mainly considered as a mediator of apoptosis in immune cells. Subsequent studies demonstrated its involvement in the development of the central nervous system, plasticity, neuronal differentiation, neurodegeneration, and brain injury. However, its role in the regulation of survival of mature CNS neurons in neuroinflammation proved controversial. This review summarizes the data on the involvement of NF-κB in the response of different brain cell types to the action of pro-inflammatory factors. Different subunits of the NF-κB family form dimers whose involvement in the regulation of gene expression depends on stimulus type. Interestingly, NF-κB is involved in the pro-inflammatory activation of microglia and astrocytes, whereas in neurons its protective or degenerative effects depend on the type of stimulus and on the time of the delayed cell response. The stimulus-dependent nature of NF-κB activation is determined by a wide range of receptors triggering a number of cell signaling cascades that terminate in the activation of the transcription factor. Tumor necrosis factor receptors (TNFR) or death receptors, Toll-like receptors (TLR), and protease-activated receptors (PAR) are among the membrane receptors capable of initiating intracellular cascades leading to the activation of NF-κB. Importantly, NF-κB activity and its effects can be modulated by other transcription factors. STAT1, STAT3, and Sirt1 are the molecules that, according to recent studies, are able to change the character of the NF-κB-mediated cellular responses. Thus, NF-κB is a transcription factor playing one of the key roles in determining the outcome of negative stimuli on the nervous system, which is why it may be considered as a pharmacological target for treating neurodegenerative processes associated with inflammation.

摘要—NF-κB 是一个核转录因子家族，在许多慢性炎症过程的发病机制和免疫反应调节中起主导作用。上世纪末，NF-κB主要被认为是免疫细胞凋亡的介质。随后的研究表明它参与了中枢神经系统的发育、可塑性、神经元分化、神经变性和脑损伤。然而，它在调节神经炎症中成熟中枢神经系统神经元存活中的作用被证明是有争议的。本综述总结了 NF-κB 参与不同脑细胞类型对促炎因子作用的反应的数据。NF-κB 家族的不同亚基形成二聚体，其参与基因表达的调节取决于刺激类型。有趣的是，NF-κB 参与小胶质细胞和星形胶质细胞的促炎激活，而在神经元中，其保护或退化作用取决于刺激类型和延迟细胞反应的时间。NF-κB 激活的刺激依赖性性质由触发许多细胞信号级联反应的广泛受体决定，这些级联反应终止于转录因子的激活。肿瘤坏死因子受体 (TNFR) 或死亡受体、Toll 样受体 (TLR) 和蛋白酶激活受体 (PAR) 是能够启动导致 NF-κB 激活的细胞内级联反应的膜受体。重要的是，NF-κB 活性及其影响可以通过其他转录因子进行调节。根据最近的研究，STAT1、STAT3 和 Sirt1 是 能够改变 NF-κB 介导的细胞反应的特征。因此，NF-κB 是一种转录因子，在确定神经系统负面刺激的结果中起着关键作用之一，这就是为什么它可以被视为治疗与炎症相关的神经退行性过程的药理学靶点。