García-Domínguez Mario
Program of Immunology and Immunotherapy, Center for Applied Medical Research University of Navarre, 31008 Pamplona, Spain.
Department of Immunology and Immunotherapy, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
Biomolecules. 2025 Aug 4;15(8):1125. doi: 10.3390/biom15081125.
S100 proteins, a family of Ca-binding proteins, play numerous roles in cellular processes such as proliferation, differentiation, and apoptosis. Recent evidence has highlighted their critical involvement in neuroinflammation, a pathological hallmark of various neurodegenerative disorders including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Among these proteins, S100B and S100A8/A9 are particularly implicated in modulating inflammatory responses in the CNS. Acting as DAMPs, they interact with pattern recognition receptors like RAGE and TLRs, triggering pro-inflammatory signaling cascades and glial activation. While low concentrations of S100 proteins may support neuroprotective functions, increased levels are often associated with exacerbated inflammation and neuronal damage. This review explores the dualistic nature of S100 proteins in neuroinflammatory processes, their molecular interactions, and their potential as biomarkers and therapeutic targets in neurodegenerative disease management.
S100蛋白是一类钙结合蛋白家族，在细胞增殖、分化和凋亡等细胞过程中发挥着多种作用。最近的证据突出了它们在神经炎症中的关键作用，神经炎症是包括阿尔茨海默病、多发性硬化症和帕金森病在内的各种神经退行性疾病的病理标志。在这些蛋白中，S100B和S100A8/A9特别参与调节中枢神经系统中的炎症反应。作为内源性危险信号，它们与RAGE和TLR等模式识别受体相互作用，触发促炎信号级联反应和胶质细胞激活。虽然低浓度的S100蛋白可能支持神经保护功能，但水平升高通常与炎症加剧和神经元损伤有关。本综述探讨了S100蛋白在神经炎症过程中的二元性、它们的分子相互作用以及它们作为神经退行性疾病管理中的生物标志物和治疗靶点的潜力。
