The key role of Piezo1 channels in ferroptosis after spinal cord injury and the therapeutic potential of Piezo1 inhibitors

• Published in: Progress in biophysics and molecular biology Vol. 196; pp. 132 - 140
• Main Authors: Li, Qianxi, Li, Chenyu, Liu, Xinyu, Guo, Zixuan, Li, Xinxin, Zhang, Xin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2025
• Subjects: Animals; Ferroptosis; Ferroptosis - drug effects; GsMTx4; Humans; Ion Channels - antagonists & inhibitors; Ion Channels - metabolism; Mechanical stress; Piezo1; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Spinal cord injury; Ferroptosis; Piezo1; Spinal cord injury; Mechanical stress; GsMTx4
• ISSN: 0079-6107; 1873-1732; 1873-1732
• DOI: 10.1016/j.pbiomolbio.2025.05.001

Ferroptosis has been confirmed to be one of the key mechanisms of neuronal injury and dysfunction after spinal cord injury (SCI). Mechanical stresses such as deformation, compression, and stretching not only directly cause physical damage to spinal cord tissue at the moment of SCI, but also promote the development of ferroptosis through various pathways. However, the mechanism of ferroptosis after SCI remains unclear, which hinders the development of therapeutic methods. This article aims to review the key mechanisms by which mechanical stress affects ferroptosis after SCI, including its impact on the structure and function of the endoplasmic reticulum (ER) and mitochondria, its role in triggering inflammatory responses, and its activation of mechanosensitive channels. Special emphasis is placed on the role of Piezo1 channels, which are key factors in cell mechanosensation and ion homeostasis regulation. The review explores how Piezo1 channels are upregulated by mechanical stress after SCI and participate in the ferroptosis process by mediating ion flow and other mechanisms. Inhibiting Piezo1 channels may be a potential therapeutic strategy for SCI. This review summarizes the therapeutic potential of Piezo1 inhibitors by sorting out existing studies, hoping to provide a theoretical basis for effective therapeutic strategies targeting ferroptosis after SCI.