Antioxidant response transcription factor nuclear factor erythroid-2-related factor 2 (Nrf2/Nfe2l2) is a neuroprotective agent in learning and memory impairment. This study provides a new perspective to explore the regulatory mechanisms of Nrf2. Here, we found that Nrf2 regulated circular RNA circ-Vps41 to increase hippocampal synaptic plasticity; Nrf2 bound the Vps41 promoter to activate transcription of the Vps41 gene and promote expression of circ-Vps41; circ-Vps41 positively correlated with Nrf2, synaptic plasticity, and learning and memory but negatively correlated with reactive oxygen species; and Nrf2 promoted CaMKIV expression by increasing levels of circ-Vps41, which can absorb miR-26a-5p that targets CaMKIV. Our findings revealed a new circRNA-based regulatory network regulated by Nrf2 and provided novel insights into the potential mechanism involved in the improvement of learning and memory impairment.

抗氧化反应转录因子核因子红细胞 2 相关因子 2 (Nrf2/Nfe2l2) 是学习和记忆障碍的神经保护剂。本研究为探索Nrf2的调控机制提供了新的视角。在这里，我们发现 Nrf2 调节环状 RNA circ-Vps41 以增加海马突触可塑性；Nrf2与Vps41启动子结合，激活Vps41基因转录，促进circ-Vps41表达；circ-Vps41与Nrf2、突触可塑性和学习记忆呈正相关，与活性氧呈负相关；Nrf2 通过增加 circ-Vps41 的水平来促进 CaMKIV 的表达，circ-Vps41 可以吸收靶向 CaMKIV 的 miR-26a-5p。