Wu Jia-Wei, Wang Bing-Xin, Shen Li-Ping, Chen Yong-Lin, Du Zhi-Yong, Du Shi-Qing, Lu Xiao-Jie, Zhao Xu-Dong
Department of Neurosurgery, Jiangnan University Medical Center, Wuxi, 214002, Jiangsu Province, China.
Wuxi Neurosurgical Institute, Wuxi, 214002, Jiangsu Province, China.
Mol Neurobiol. 2025 Mar 18. doi: 10.1007/s12035-025-04834-4.
Cerebrovascular disease (CVD) is a significant neurological condition resulting from pathological changes in the brain's blood supply and is currently the leading cause of death and disability worldwide. The progression of CVD is closely associated with endothelial damage, plaque formation, and thrombosis, driven by long-term alterations in vascular endothelial cells, smooth muscle cells, microglia, and other immune-inflammatory cells. Among the key molecular pathways involved, the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway plays a central role. Dysregulation of the JAK-STAT pathway is implicated in the pathogenesis of CVD by influencing the aforementioned cell types and associated pathological processes. Importantly, the role of the JAK-STAT pathway varies across different types of CVD and throughout different stages of disease progression (e.g., pre-morbid, acute, and chronic phases). This review examines the composition, activation, and regulation of the JAK-STAT pathway and summarizes recent findings on its involvement in CVD. We discuss the distinct roles of JAK-STAT signaling in various CVD conditions, the potential reasons for these differences, and explore the clinical translational prospects and technical challenges of targeting the JAK-STAT pathway for therapeutic intervention in CVD.
脑血管疾病（CVD）是一种由脑部血液供应的病理变化引起的重要神经系统疾病，目前是全球死亡和残疾的主要原因。CVD的进展与内皮损伤、斑块形成和血栓形成密切相关，这些是由血管内皮细胞、平滑肌细胞、小胶质细胞和其他免疫炎症细胞的长期变化驱动的。在涉及的关键分子途径中，Janus激酶/信号转导子和转录激活子（JAK-STAT）信号通路起着核心作用。JAK-STAT通路的失调通过影响上述细胞类型和相关病理过程，参与了CVD的发病机制。重要的是，JAK-STAT通路的作用在不同类型的CVD以及疾病进展的不同阶段（如病前、急性和慢性阶段）有所不同。本综述探讨了JAK-STAT通路的组成、激活和调节，并总结了其参与CVD的最新研究结果。我们讨论了JAK-STAT信号在各种CVD情况下的不同作用、这些差异的潜在原因，并探讨了针对JAK-STAT通路进行CVD治疗干预的临床转化前景和技术挑战。
