Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (8): 2231-2244.doi: 10.4103/NRR.NRR-D-24-00119

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C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Xiangzi Wang1, #, Xiaofei Niu2 #, Yingkai Wang1 , Yang Liu1 , Cheng Yang3, *, Xuyi Chen3, *, Zhongquan Qi1, 4, *   

  1. 1 School of Medicine, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, China;  2 Graduate School of Tianjin University of Traditional Chinese Medicine, Tianjin, China;  3 Characteristic Medical Center of People’s Armed Police Forces, Tianjin, China;  4 Fujian Maternity and Child Health Hospital, Fuzhou, Fujian Province, China
  • Online:2025-08-15 Published:2024-12-12
  • Contact: Cheng Yang, MD, poweryc@126.com; Zhongquan Qi, MD, yxyyz@gxu.edu.cn; Xuyi Chen, MD, chenxuyi1979@126.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China (Key Program), No. 11932013; the National Natural Science Foundation of China (General Program), No. 82272255; Armed Police Force High-Level Science and Technology Personnel Project; The Armed Police Force Focuses on Supporting Scientific and Technological Innovation Teams; and Key Project of Tianjin Science and Technology Plan, No. 20JCZDJC00570 (all to XC).

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Abstract: Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage. The expression of the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis exhibits significant differences before and after injury. Recent studies have revealed that the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury, suggesting that this axis is a novel target and regulatory control point for treatment. This review comprehensively examines the therapeutic strategies targeting the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis, along with the regenerative and repair mechanisms linking the axis to spinal cord injury. Additionally, we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C–C motif chemokine ligand 2/ C–C motif chemokine receptor 2 axis. This review primarily elaborates on therapeutic strategies that target the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs, along with the approaches used to exploit new therapeutic targets within the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis and the development of targeted drugs. Nevertheless, there are presently no clinical studies relating to spinal cord injury that are focusing on the C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 axis. This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury. 

Key words: apoptosis, C–C motif chemokine ligand 2/C–C motif chemokine receptor 2 pathway, C–C motif chemokine receptor 2 antagonists, chemokine ligand 2, chemokine receptor 2, inflammation, macrophage, microglia, spinal cord injury, therapeutic method