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-β (Aβ). 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 Aβ. Activity and phagocytosis were assessed using CCK8 and flow cytometry. SMOC2 mRNA levels were quantified by qPCR, and protein levels of SMOC2, TGF-β1, p-NF-κB/NF-κB were analyzed by western blot. Aβ content was determined by ELISA, and immunofluorescence detected TNF-α, IL-1β, CD163, and CD206. Results Aβ treatment inhibited microglial activity and phagocytosis, but SMOC2 disruption enhanced these functions (p < 0.05). SMOC2 overexpression increased its expression and Aβ levels, while interference reduced them (p < 0.001). SMOC2 overexpression also decreased TGF-β1, CD163, and CD206, and increased p-NF-κB/NF-κB, TNF-α, and IL-1β (p < 0.05). Conclusions SMOC2 plays a crucial role in microglial cell activity, phagocytosis, and polarization, potentially through the TGF-β1/NF-κB pathway, offering insights into AD pathogenesis.