Sirtuin1 in Spinal Cord Injury: Regulatory Mechanisms, Microenvironment Remodeling and Therapeutic Potential

作者：Jinze Li, Shengyu Cui, Yanqiu Li, Can Zhang, Chao Chang, Fengzeng Jian · 发表于：CNS Neuroscience & Therapeutics · 年份：2025 · DOI：10.1111/cns.70244 · 被引用次数：10 · 研究领域：Sirtuins and Resveratrol in Medicine、Nerve injury and regeneration、Spinal Cord Injury Research

BACKGROUND: -dependent deacetylase, has emerged as a promising therapeutic target for SCI repair due to its potential to protect neurons, regulate glial and vascular cells, and optimize the injury microenvironment. However, the regulatory roles of Sirt1 in SCI are complex and challenging, as its effects vary depending on activation timing, expression levels, and cell types. METHODS: A systematic literature review was conducted using PubMed, Scopus, and Web of Science to identify studies investigating Sirt1 in SCI. Relevant publications were analyzed to synthesize current evidence on Sirt1's mechanisms, therapeutic effects, and challenges in SCI repair. RESULTS: Sirt1 exerts broad regulatory effects across diverse pathological processes and cell types post-SCI. It promotes neuronal survival and axonal regeneration, modulates astrocytes and microglia to resolve inflammation, supports oligodendrocyte-mediated myelination, and enhances vascular endothelial function. Proper Sirt1 activation may mitigate secondary injury, whereas excessive or prolonged activation could impair inflammatory resolution or disrupt cellular homeostasis. This review highlights Sirt1 activation as potential therapies, but challenges include optimizing spatiotemporal activation and addressing dual roles in different cell types. CONCLUSION: Targeting Sirt1 represents a viable strategy for SCI repair, given its multifaceted regulation of neuroprotection, immunomodulation, and tissue remodeling. However, tran...