Fan Baoyou, Liu Derong, Qin Jia, Shi Zhongju, Hu Zicheng, Gao Xiang, Ren Yifei, Zhao Pengtian, Chen Xiaoyang, Ren Yiming, Ning Guangzhi, Liu Tao, Feng Shiqing
Department of Othopaedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, PR China; International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, PR China.
Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guizhou Hospital, No.58 Zhongshan Er Road, Guangzhou, Guangdong Province, 510080, PR China.
Free Radic Biol Med. 2025 Feb 1;227:129-142. doi: 10.1016/j.freeradbiomed.2024.11.052. Epub 2024 Dec 1.
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.
铁死亡已被证明与脊髓损伤（SCI）的进展有关。铁死亡抑制蛋白1（FSP1）可与谷胱甘肽过氧化物酶4（GPX4）并行抑制铁死亡。然而，FSP1在脊髓损伤发病机制中的作用尚不清楚。研究发现，在脊髓损伤后的急性期和亚急性期，FSP1的蛋白和基因水平均下调。FSP1敲低实验表明，FSP1除了通过介导辅酶Q调节铁死亡外，还通过调节细胞内稳态和金属离子反应系统影响铁死亡敏感性。此外，艾地苯醌（IDE）被鉴定为一种铁死亡抑制剂。研究表明，即使FSP1被敲低，IDE也能抑制活性氧（ROS）并恢复GPX4和xCT的表达，从而抑制少突胶质细胞的铁死亡。体内实验结果表明，IDE能有效挽救少突胶质细胞和神经元免于铁死亡，促进损伤脊髓的髓鞘形成，促进组织修复和功能恢复。本研究为通过调节铁死亡中的FSP1修复脊髓损伤提供了一种新策略。
