Research Progress on miRNA Regulation of Ferroptosis in Epilepsy-Associated Neurons
YANG Xun1#, YUAN Ziao2#, DUN Yuanyuan1, ZHU Jinling1*
Recent studies have demonstrated that miRNAs (microRNAs) play a pivotal role in the pathogenesis of epilepsy by regulating ferroptosis, particularly in core processes such as modulating the system Xc–/GSH/GPX4 antioxidant axis, iron homeostasis, and lipid peroxidation. Research has shown that in epilepsy-related animal models, upregulated expression of miR-34a-5p targets SIRT1/GPX4 signaling axis to mediate the Wnt/β-catenin pathway, promoting lipid peroxidation and ferroptosis, thereby exacerbating neuronal damage. Conversely, downregulated expression of miR-211-5p targets P2RX7 to modulate the GPX4/HO-1 axis via the MAPK/ERK pathway, thereby inhibiting ferroptosis and ameliorating epileptic phenotypes. Additionally, miRNAs interact with various stress and transcription factor networks (e.g., Nrf2, p53, MAPK/ERK) to further regulate neuronal susceptibility to ferroptosis. Given that miRNAs are not only critical regulators of neuronal apoptosis, excitatory/inhibitory balance, and synaptic plasticity but also deeply involved in the occurrence and progression of ferroptosis, this article focuses on differentially expressed miRNAs validated through epilepsy animal models and in vitro neuronal cell experiments, analyzing their causal relationships with ferroptosis. The aims are to provide new insights into the pathophysiological processes of epilepsy and to provide a theoretical basis for the future development of new targets for epilepsy treatment.
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