Ferroptosis has been demonstrated to be involved in the progression of spinal cord injury (SCI). Ferroptosis suppressor protein 1 (FSP1) can inhibit ferroptosis in parallel with Glutathione peroxidase 4 (GPX4). However, the role of FSP1 in the pathogenesis of spinal cord injury is unclear. The protein and gene levels of FSP1 were found to be downregulated during both the acute and subacute stages after SCI. In addition to regulating ferroptosis by mediating CoQ, FSP1 also influences ferroptosis sensitivity by modulating cellular homeostasis and the metal ion response system, as demonstrated by FSP1 knockdown experiments. Furthermore, Idebenone (IDE) was identified as a ferroptosis inhibitor. IDE was shown to inhibit reactive oxygen species (ROS) and restore the expression of GPX4 and xCT, thereby suppressing ferroptosis of oligodendrocytes, even when FSP1 was knocked down. In vivo results indicated that IDE could effectively rescue oligodendrocytes and neurons from ferroptosis, promoting myelination of the injured spinal cord and facilitating tissue repair and functional recovery. This study provides a novel strategy for repairing SCI through the regulation of FSP1 in ferroptosis.
Keywords: COQ10; FSP1; Ferroptosis; Idebenone; Spinal cord injury.
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