NOP58 knockdown in microglia is associated with reduced neuroinflammation and synaptic damage in NMOSD

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory demyelinating disease of the central nervous system. This study investigated the role of nucleolar protein 58 (NOP58) in NMOSD pathogenesis, focusing on microglia-mediated neuroinflammation and synaptic damage.

Differentially expressed genes were obtained from the GSE235276 dataset to identify hub genes via support vector machine-recursive feature elimination and protein-protein interaction networks. Diagnostic performance was validated using receiver operating characteristic analysis based on the GSE235277 dataset. BV2 cells treated with serum from NMOSD patients were co-cultured with primary cortical neurons. Molecular effects of NOP58 silencing were assessed using real-time quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay for inflammatory cytokines, microglial activation markers, and synaptic markers.

RNA binding motif protein 28 (RBM28) and NOP58 were identified as candidate hub genes with potential diagnostic value. Both were upregulated in BV2 cells treated with NMOSD serum and confirmed in serum-derived RNA from NMOSD patients. The treatment of the serum from patients with NMOSD significantly increased pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor-α) and the expression of Iba1 in BV2 cells. NOP58 expression positively correlated with these cytokines. NOP58 silencing reduced cytokine levels, restored postsynaptic density protein 95 (PSD95) and synapsin-1 in co-cultured neurons, and decreased interleukin-17 A (IL-17 A) and nuclear factor-κB (NF-κB) activator 1 (ACT1) levels, suggesting involvement of IL-17 signaling.

Knockdown of NOP58 in BV2 cells reduces neuroinflammation and synaptic damage in co-cultured neurons, highlighting its potential as a candidate therapeutic target in NMOSD.