The pathological hallmarks of Parkinson's disease (PD) are the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of overactivated glial cells and neuroinflammation. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) c-Rel subunit is closely related in the pathological progress of PD, however the roles and mechanisms of c-Rel in PD development remain unclear. Here, in neurotoxins-induced PD models, the dynamic changes of NF-κB c-Rel and its functions were evaluated. We found that c-Rel was rapidly activated in the nigrostriatal pathway, which mainly occurred in dopaminergic neurons and microglia. c-Rel could maintain neuronal survival by initiating the anti-apoptotic gene expression in MPP⁺-treated SH-SY5Y cells and it could inhibit microglial overactivation by suppressing the inflammatory gene expression in LPS-challenged BV2 cells. c-Rel inhibitor IT901 aggravated the damage of MPTP on dopaminergic neurons and promoted the activation of microglia in the nigrostriatal pathway of mice. Moreover, the expression of c-Rel in blood samples of PD patients decreased dramatically. Our results indicate that the NF-κB/c-Rel subunit plays an important role in neuroprotection and neuroinflammation inhibition during PD progression.

帕金森病 (PD) 的病理特征是黑质致密部 (SNpc) 中多巴胺能 (DA) 神经元的逐渐丧失以及过度活化的神经胶质细胞和神经炎症的存在。活化B细胞核因子κ-轻链增强子（NF-κB）c-Rel亚基与PD的病理进展密切相关，但c-Rel在PD发生发展中的作用和机制尚不清楚。在这里，在神经毒素诱导的 PD 模型中，评估了 NF-κB c-Rel 的动态变化及其功能。我们发现 c-Rel 在黑质纹状体通路中被迅速激活，主要发生在多巴胺能神经元和小胶质细胞中。c-Rel 可以通过启动 MPP ^{+ 中}的抗凋亡基因表达来维持神经元存活处理的 SH-SY5Y 细胞，它可以通过抑制 LPS 攻击的 BV2 细胞中的炎症基因表达来抑制小胶质细胞过度活化。c-Rel抑制剂IT901加重了MPTP对多巴胺能神经元的损伤，促进了小鼠黑质纹状体通路中小胶质细胞的活化。此外，PD患者血样中c-Rel的表达显着下降。我们的结果表明，NF-κB/c-Rel 亚基在 PD 进展过程中的神经保护和神经炎症抑制中发挥重要作用。