SMOC2 promotes microglia activity and neuroinflammation in Alzheimer's disease

Background Alzheimer's disease (AD), the leading cause of dementia, is characterized by cognitive decline and the accumulation of amyloid-beta (A beta). It affects millions, with numbers expected to double by 2050. SMOC2, implicated in inflammation and fibrosis, may play a role in AD pathogenesis, particularly in microglial cell function, offering a potential therapeutic target. Objective Alzheimer's disease (AD) leads to neurodegeneration, affecting cognition, language, and personality, underscoring the urgency for effective treatments. Our study investigates the role of secreted modular calcium-binding protein 2 (SMOC2) in microglial cells and its impact on AD pathology. Methods We introduced SMOC2 overexpression and interference vectors into microglial cells treated with A beta. Activity and phagocytosis were assessed using CCK8 and flow cytometry. SMOC2 mRNA levels were quantified by qPCR, and protein levels of SMOC2, TGF-beta 1, p-NF-kappa B/NF-kappa B were analyzed by western blot. A beta content was determined by ELISA, and immunofluorescence detected TNF-alpha, IL-1 beta, CD163, and CD206. Results A beta treatment inhibited microglial activity and phagocytosis, but SMOC2 disruption enhanced these functions (p < 0.05). SMOC2 overexpression increased its expression and A beta levels, while interference reduced them (p < 0.001). SMOC2 overexpression also decreased TGF-beta 1, CD163, and CD206, and increased p-NF-kappa B/NF-kappa B, TNF-alpha, and IL-1 beta (p < 0.05). Conclusions SMOC2 plays a crucial role in microglial cell activity, phagocytosis, and polarization, potentially through the TGF-beta 1/NF-kappa B pathway, offering insights into AD pathogenesis.