Zhang Qiu-Xia, Zhang Lin-Jie, Zhao Ning, Yang Li
Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Front Pharmacol. 2025 Apr 29;16:1561939. doi: 10.3389/fphar.2025.1561939. eCollection 2025.
Multiple sclerosis is a chronic autoimmune demyelinating disorder predominantly affecting the white matter of the central nervous system, with experimental autoimmune encephalomyelitis (EAE) serving as its classical animal model. Irisin, a glycosylated protein derived from the proteolytic cleavage of fibronectin type III domain-containing protein 5, plays a significant role in metabolic regulation and inflammatory modulation within the organism.
In this study, we systematically investigated the therapeutic effects and underlying mechanism of Irisin on EAE and BV2 microglial cells through comprehensive methodologies including quantitative real-time polymerase chain reaction, immunofluorescence staining and western blot.
Irisin exerts neuroprotective effects in EAE mice, significantly ameliorating both clinical and pathological manifestations of the disease. Mechanistically, Irisin attenuated inflammatory response and reduced the number of microglia through NF-κBp65 signaling pathway.
In conclusion, these results collectively suggest that Irisin alleviates EAE progression by suppressing microglia activation via the NF-κBp65 pathway, highlighting its potential as a promising therapeutic target for multiple sclerosis treatment.
多发性硬化症是一种慢性自身免疫性脱髓鞘疾病，主要影响中枢神经系统的白质，实验性自身免疫性脑脊髓炎（EAE）是其经典的动物模型。鸢尾素是一种由含III型纤连蛋白结构域蛋白5经蛋白水解裂解产生的糖蛋白，在机体的代谢调节和炎症调节中发挥重要作用。
在本研究中，我们通过定量实时聚合酶链反应、免疫荧光染色和蛋白质印迹等综合方法，系统地研究了鸢尾素对EAE和BV2小胶质细胞的治疗作用及潜在机制。
鸢尾素对EAE小鼠具有神经保护作用，显著改善了该疾病的临床和病理表现。从机制上讲，鸢尾素通过NF-κBp65信号通路减轻炎症反应并减少小胶质细胞数量。
总之，这些结果共同表明，鸢尾素通过NF-κBp65途径抑制小胶质细胞活化，从而减轻EAE的进展，突出了其作为多发性硬化症治疗有前景的治疗靶点的潜力。
