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Updated: Jan 9, 2026
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
Integrated Bioinformatics Identifies NLRP3 Inflammasome Hub Genes and Therapeutic Targets in Schizophrenia
Jiawei Ma1, Yongchun Cui1, Xinying Li2
1Department of Psychiatry, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, People's Republic of China.
Background:
The pathogenesis of schizophrenia (SZ) remains incompletely understood; although neuroinflammation and the NLRP3 inflammasome have been implicated, the key regulatory genes involved are still unidentified.
Objective:
To investigate the association between SZ and NLRP3 inflammasome-related genes, and to screen for hub genes as potential biomarkers and therapeutic targets.
Methods:
We analyzed the GEO dataset GSE27383, comprising 43 SZ patients and 29 controls, and identified 1,672 differentially expressed genes (DEGs). NLRP3-related genes were obtained from GeneCards, and weighted gene co-expression network analysis (WGCNA) highlighted the green, yellow, and red modules. The intersection of DEGs, NLRP3-related genes, and module genes was further refined using LASSO and Random Forest algorithms. Immune cell infiltration was profiled with CIBERSORT, and the diagnostic utility of candidate genes was evaluated using ROC curves. Molecular docking was performed to predict compound binding, and hub gene expression was validated in an independent cohort of 20 SZ patients and 20 controls using RT-qPCR on PBMCs.
Results:
Five hub genes-HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS-were significantly down-regulated in SZ (P < 0.05). The combined ROC-AUC reached 0.883. Molecular docking revealed strong binding affinities of ellagic acid to FLNA (-4.70 kcal mol- 1), and of hydralazine to HSPA8 (-4.27), TRAF2 (-4.84), and SCAP (-4.98). Differential expression was confirmed in PBMCs. Additionally, SZ patients exhibited increased naive B cells and neutrophils, along with reduced resting NK cells and M2 macrophages.
Conclusion:
Five genes (HSPA8, SCAP, FLNA, TRAF2, PINK1-AS) were identified as potential novel biomarkers and therapeutic targets for SZ, providing a theoretical foundation for elucidating disease mechanisms and advancing precision medicine in SZ.
