Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (7): 3114-3121.doi: 10.4103/NRR.NRR-D-24-00890

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Targeting JNK1 mediates alleviation of neuroinflammation and promotes neural repair by cerebral dopamine neurotrophic factor after spinal cord injury

Yanxiao Xiang1, #, Pengchao Du2, #, Yayun Zhang3, Hao Li4, Songgang Wang4, Xianlei Gao4, Xin Pan4, Hua Zhao4, *   

  1. 1Department of Pharmacy, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; 
    2School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong Province, China; 
    3Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China;
    4Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
  • Online:2026-07-15 Published:2026-04-01
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81601067 (to HZ); and Shandong Natural Science Foundation of Shandong Province, Nos. ZR2021MH134 (to HZ) and ZR2020MH080 (to PD).

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Abstract: Previous studies have shown that endoplasmic reticulum stress induces neuronal apoptosis, necrosis, and pro-inflammatory microenvironment after spinal cord injury. The JNK pathway is activated by endoplasmic reticulum stress and reactive oxygen species. Our previous research demonstrated that cerebral dopamine neurotrophic factor has anti-inflammatory effects and promotes the repair of the damaged spinal cord after injury. However, the molecular mechanism remains unclear. In this study, we found that cerebral dopamine neurotrophic factor binds JNK1 and regulates JNK1/2-c-Jun-p53 signaling in lipopolysaccharide-induced microglia. Cerebral dopamine neurotrophic factor also alleviated neuroinflammation by reducing the secretion of pro-inflammatory cytokines. Overexpression of cerebral dopamine neurotrophic factor in a mouse model of spinal cord injury promoted nerve regeneration and motor function recovery. These findings indicate the possibility for cerebral dopamine neurotrophic factor treating spinal cord injury by targeting the JNK1/2-c-Jun-p53 pathway. 

Key words: cerebral dopamine neurotrophic factor, ER stress, JNK1, microenvironment, microglia, nerve repair, neural regeneration, neuroinflammation, proinflammatory cytokine, spinal cord injury