REVIEW article
Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1624501
Sonic Hedgehog Signaling in Spinal Cord Injury: Mechanisms and Therapeutic Implications
Provisionally accepted
- 1Department of Emergency, Taizhou Integrated Chinese and Western Medicine Hospital, Taizhou, Zhejiang 317523, China
- 2Department of Emergency, The First People's Hospital of Linhai, Taizhou, Zhejiang 317000, China
- 3Longquan People's Hospital, Lishui, China
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Spinal cord injury is a serious neurological condition that results in severe dysfunction below the level of injury, often leading to long-term disability and impaired quality of life. Despite significant advances in medical care, effective treatment options remain limited. Recent research has highlighted the role of endogenous signaling pathways, including Sonic Hedgehog, in the natural healing response following SCI. Sonic Hedgehog (Shh) signaling pathway plays a vital role in spinal cord development and post-injury regeneration by regulating neuroprotection, axon regeneration, synaptic remodeling and inflammation. Shh exerts its effects through a well-defined cascade involving Patched (Ptch), Smoothened (Smo) and Gli transcription factors, ultimately influencing genes involved in neural repair. Various pharmacological agents including agonists (SAG, Purmorphamine and Shh-N) and antagonists (Cyclopamine, Vismodegib and Sonidegib) have been studied for their ability to modulate this pathway and enhance recovery in preclinical models. In addition, emerging approaches such as stem cell therapies, exosome delivery and nanotechnology-based drug targeting are under investigation to improve the efficacy and specificity of Shh-based treatments. However, despite promising experimental outcomes, the clinical translation of these findings faces significant challenges, including delivery limitations, potential tumorigenicity, immune variability and the lack of robust human data. This review critically examines the molecular mechanisms and therapeutic potential of Shh signaling in SCI, highlights current limitations and conflicting evidence and outlines future directions to bridge the gap between preclinical findings and clinical application.
Keywords: Gli transcription factors, Neuron, SMO, Sonic hedgehog signaling pathway, spinal cord injury
Received: 07 May 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 Du, Chen and Ji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaozhen Ji, Longquan People's Hospital, Lishui, China
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