2. Academic Validation
  3. Ferroptosis suppressor protein 1 regulated oligodendrocytes ferroptosis rescued by idebenone in spinal cord injury

Ferroptosis suppressor protein 1 regulated oligodendrocytes ferroptosis rescued by idebenone in spinal cord injury

  • Free Radic Biol Med. 2025 Feb 1:227:129-142. doi: 10.1016/j.freeradbiomed.2024.11.052.
Baoyou Fan 1,  Derong Liu 1,  Jia Qin 2,  Zhongju Shi 1,  Zicheng Hu 1,  Xiang Gao 1,  Yifei Ren 1,  Pengtian Zhao 1,  Xiaoyang Chen 1,  Yiming Ren 1,  Guangzhi Ning 1,  Tao Liu 3,  Shiqing Feng 4
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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. Electronic address: liu_tao_tj@163.com.
  • 4 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. Electronic address: sqfeng@tmu.edu.cn.
PMID: 39626861 DOI: 10.1016/j.freeradbiomed.2024.11.052
Abstract

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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