Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (6): 2124-2140.doi: 10.4103/NRR.NRR-D-24-01239

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Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights

Nuokun Li1, #, Shiyi Wen2, #, Dandan Li3 , Yaning Shi1 , Zhigang Mei4 , Danhong Liu4 , Hui Yang5 , Yuhong Wang1 , Xiaoyuan Lin5 , Yun Xiang1, *, Hongbo Wen6, *, Pan Meng1, 4, *   

  1. 1 Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, China;  2 Department of Plastic Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China;  3 Department of Science and Technology, Hunan University of Chinese Medicine, Changsha, Hunan Province, China;  4 School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China;  5 The First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan Province, China;  6 Department of Neurosurgery, Yiyang Central Hospital of Hunan Province, Yiyang, Hunan Province, China
  • Online:2026-06-15 Published:2025-09-16
  • Contact: Hongbo Wen, MS, docwhbo@163.com; Yun Xiang, MS, xiangyun003997@hnucm.edu.cn; Pan Meng, MD, 004181@hnucm.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82474468 (to PM); the Science and Technology Innovation Program of Hunan Province, No. 2024RC3200 (to PM); the Health Commission Talent Project of Hunan Province, No. 20240304118 (to PM); the Scientific Research Project of Hunan Department of Education, No. 23A0281 (to PM); the Open Fund for Chinese Medicine Powder and Innovative Drugs in the Cultivation Base of the ProvincialMinistry Jointly Established State Key Laboratory of Chinese Medicine, No. 23PTKF1013 (to PM); and the Training Plan of Outstanding Innovative Youth of Changsha, No. kq2009018 (to PM).

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Abstract: Over the past few decades, the Sonic Hedgehog protein has become a pivotal player in many biological processes, including tumourigenesis, embryonic development, and protective mechanisms after cerebral damage. The Sonic Hedgehog signaling pathway is crucial in the central nervous system, with implications in a diverse range of diseases, including Parkinson’s disease, Alzheimer’s disease, spinal cord injury, traumatic brain injury, depression, Sonic Hedgehog medulloblastoma, and stroke. In this comprehensive review, we examined Sonic Hedgehog from the perspective of canonical and non-canonical pathways, elucidating their complex connections to the central nervous system. Subsequently, we summarize the latest advancements in drug therapies that offer novel strategies for treating neurological diseases by modulating the Sonic Hedgehog protein. Finally, we summarize and extend the technologies and tools for studying the Sonic Hedgehog signaling field, with the aim of providing new research ideas and methods.

Key words: Alzheimer’s disease, canonical, central nervous system disease, drug therapy, neural regeneration, non-canonical, Sonic Hedgehog, Sonic Hedgehog medulloblastoma, stroke