靶向甲酰基肽受体1减少脑炎症和神经变性，这一成果由
在多发性硬化症患者中，课题组人员发现甲酰基肽受体1 （FPR1）在中枢神经系统（CNS）常驻小胶质细胞和中枢神经系统浸润性巨噬细胞中的表达增加。N-甲酰化肽是FPR1的内源性激动剂，其血液量与MS患者的疾病进展相关。在MS motheme模型中，通过FPR1传递的信号可促进小胶质细胞线粒体功能障碍、导管轴突丢失和细胞凋亡。表达FPR1的小胶质细胞抑制了髓磷脂反应性CD4+ T细胞在中枢神经系统中的克隆扩增。一种穿透中枢神经系统的小分子FPR1拮抗剂T0080可减轻自身免疫反应和轴突变性。他们的研究确定FPR1信号是MS进展的潜在机制，并建议拮抗FPR1作为治疗方法。
研究人员表示，多发性硬化症（MS）通过大脑区域特异性炎症和变性进展，机制尚不明确。
附：英文原文
Title: Targeting formyl peptide receptor 1 reduces brain inflammation and neurodegeneration
Author: Yulin Li, Zhiguo Li, Pei Zheng, Shuzhen Guan, Yan Li, Nan Yao, Zhihui Qi, Xueyu Zhang, Lei Su, Jing Jing, Siting Wu, Xue Zhao, Meng Wang, Chotima Bttcher, Hans-Gustaf Ljunggren, Friedemann Paul, Luc Van Kaer, Alexei Verkhratsky, Fu-Dong Shi
Issue&Volume: 2025-11-13
Abstract: Multiple sclerosis (MS) progresses through brain region–specific inflammation and degeneration, with poorly defined mechanisms. In individuals with MS, we identified increased expression of formyl peptide receptor 1 (FPR1) in central nervous system (CNS)–resident microglia and CNS-infiltrating macrophages. Blood amounts of N-formylated peptides, which are endogenous agonists of FPR1, correlated with disease progression in patients with MS. In MS mouse models, signaling through FPR1 promoted microglial mitochondrial dysfunction, causing axonal loss and apoptosis. FPR1-expressing microglia sustained the clonal expansion of myelin-reactive CD4+ T cells in the CNS. A CNS-penetrating small molecule FPR1 antagonist, T0080, mitigated autoimmune responses and axonal degeneration. Our study identifies FPR1 signaling as a potential mechanism for MS progression and suggests antagonizing FPR1 as a therapeutic approach.
DOI: adq1177
Source: https://www.science.org/doi/10.1126/science.adq1177