Paclitaxel Induces Neurotoxicity via Activating Ferroptosis by Suppressing Nrf2/SLC7A11/GSH/GPX4 Signaling

• Paclitaxel induces ferroptosis in neuronal cells, characterized by mitochondrial fragmentation, increased ROS and iron levels, and decreased GSH. • RNA-seq and GSEA analyses identify ferroptosis as a key pathway in paclitaxel-induced neurotoxicity. • Paclitaxel suppresses the Nrf2/SLC7A11/GSH/GPX4 signaling pathway, a critical anti-ferroptotic defense. • Ferroptosis inhibitors like liproxstatin-1 can rescue paclitaxel-induced neuronal cell death, suggesting therapeutic potential.