中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 3114-3121.doi: 10.4103/NRR.NRR-D-24-00890

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

脑多巴胺神经营养因子治疗脊髓损伤：靶向JNK1介导神经炎症缓解和神经修复

  

  • 出版日期:2026-07-15 发布日期:2026-04-01

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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摘要：

研究显示，内质网应激可诱导脊髓损伤后神经细胞凋亡、坏死和促炎微环境，而JNK通路被内质网应激和活性氧激活。作者既往研究已发现，脑多巴胺神经营养因子具有抗炎和促进脊髓修复的作用，但其分子机制尚不清楚。此次实验发现，脑多巴胺神经营养因子可与JNK1结合，并调节JNK1/2-2-Jun-P53信号传导。脑多巴胺神经营养因子还能竞争性结合JNK1，并通过减少脂多糖诱导的小胶质细胞模型中促炎性细胞因子的分泌，减轻神经炎症。进一步在脊髓损伤小鼠模型中可见，以慢病毒过表达脑多巴胺神经营养因子可促进小鼠损伤部位神经的再生和运动功能的恢复。由此可见，脑多巴胺神经营养因子可通过特异性靶向JNK1/2-c-Jun-P53通路治疗脊髓损伤。


https://orcid.org/0000-0002-4556-5481 (Hua Zhao)

关键词: JNK1, 脊髓损伤, 内质网应激, 脑多巴胺神经营养因子, 神经炎症, 神经再生, 神经修复, 小胶质细胞, 微环境, 促炎细胞因子

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