2. Academic Validation
  3. 20-Deoxyingenol Activates Mitophagy Through TFEB and Promotes Functional Recovery After Spinal Cord Injury

20-Deoxyingenol Activates Mitophagy Through TFEB and Promotes Functional Recovery After Spinal Cord Injury

  • Mol Neurobiol. 2024 Jun 12. doi: 10.1007/s12035-024-04283-5.
Chenyu Wu # 1 2 3,  Yu Chen # 1 2 3,  Ximiao Chen # 1 2 3,  Yekai Zhang 1 2 3,  Xiaoying Zhao 1 2 3,  Yuxin Deng 1 2 3,  Chenchao Li 1 2 3,  Di Zhang 4 5 6,  Xiaolei Zhang 7 8 9,  Sheng Wang 10 11 12
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou, China.
  • 2 Zhejiang Provincial Key Laboratory of Orthopedics, Zhejiang Province, Wenzhou, China.
  • 3 The Second School of Medicine, Wenzhou Medical University, Zhejiang Province, Wenzhou, China.
  • 4 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou, China. zhangdi@wmu.edu.cn.
  • 5 Zhejiang Provincial Key Laboratory of Orthopedics, Zhejiang Province, Wenzhou, China. zhangdi@wmu.edu.cn.
  • 6 The Second School of Medicine, Wenzhou Medical University, Zhejiang Province, Wenzhou, China. zhangdi@wmu.edu.cn.
  • 7 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou, China. zhangxiaolei@wmu.edu.cn.
  • 8 Zhejiang Provincial Key Laboratory of Orthopedics, Zhejiang Province, Wenzhou, China. zhangxiaolei@wmu.edu.cn.
  • 9 The Second School of Medicine, Wenzhou Medical University, Zhejiang Province, Wenzhou, China. zhangxiaolei@wmu.edu.cn.
  • 10 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, Wenzhou, China. wangthomas2002@163.com.
  • 11 Zhejiang Provincial Key Laboratory of Orthopedics, Zhejiang Province, Wenzhou, China. wangthomas2002@163.com.
  • 12 The Second School of Medicine, Wenzhou Medical University, Zhejiang Province, Wenzhou, China. wangthomas2002@163.com.
  • # Contributed equally.
PMID: 38865079 DOI: 10.1007/s12035-024-04283-5
Abstract

Spinal cord injury (SCI) can lead to permanent paralysis and various motor, sensory and autonomic nervous system dysfunction. The complex pathophysiological processes limit the effectiveness of many clinical treatments. Mitochondria has been reported to play a key role in the pathogenesis of SCI; while Mitophagy is a protective mechanism against mitochondrial dysfunction. However, there is recently little drugs that may targeted activate Mitophagy to treat SCI. In this study, we evaluated the role of 20-Deoxyingenol (20-DOI) in SCI and explored its potential mechanisms. We used a SCI rat model and evaluated the functional outcomes after the injury. Western blotting and immunofluorescence techniques were used to analyze the levels of Mitophagy, Apoptosis, and TFEB-related signaling pathways. Our research results show that 20-DOI significantly improves the Apoptosis of neural cells after TBHP stimulation and functional recovery after spinal cord injury. In addition, Mitophagy, TFEB levels, and Apoptosis are related to the mechanism of 20-DOI treatment for spinal cord injury. Specifically, our research results indicate that 20-DOI restored the autophagic flux after injury, thereby inducing Mitophagy, eliminating the accumulation of Cyto C, and inhibiting Apoptosis. Further mechanism research suggests that 20-DOI may regulate Mitophagy by promoting TFEB nuclear translocation. These results indicate that 20-DOI can significantly promote recovery after spinal cord injury, which may be a promising treatment method for spinal cord injury.

Keywords

20-Deoxyingenol; Apoptosis; Autophagy; Mitophagy; Spinal cord injury; TFEB.

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