Critical role of Oas1g and STAT1 pathways in neuroinflammation: insights for Alzheimer’s disease therapeutics

• DOI: 10.1186/s12967-025-06112-2
• Publication Date: 2025-02-14T18:02:35Z
• Authors: Zhixin Xie; Linxi Li; Weizhong Hou; Zhongxi Fan; Lifan Zeng; Limin He; Yunxiang Ji; Jingbai Zhang; Fangran Wang; Zhou Xing; Yezhong Wang; Yongyi Ye
• Keywords: Neuroinflammation; WGCNA; Machine learning; R; Medicine; Oas1g; Alzheimer’s disease; Interferon-stimulated genes

Alzheimer's disease (AD) has a significant impact on an individual's health and places heavy burden society. Studies have emphasized the importance of microglia in progression development AD. Interferon responses Interferon-stimulated genes (ISGs) significantly function neuroinflammatory neurodegenerative diseases involving Therefore, further exploration relationship among microglia, ISGs, neuroinflammation AD is warranted. Microglia datasets from GEO database were retrieved, along with additional RNA-seq data laboratory mice. Weighted Correlation Network Analysis was used training dataset to identify gene co-expression networks. Genes black module intersected interferon-stimulated genes, differentially expressed (DEGs) identified. Machine learning algorithms applied DEGs, selected by both methods identified as hub ROC curves evaluate their diagnostic accuracy. Gene Set Enrichment performed reveal functional pathways closely relating genes. cells transfected siRNAs targeting Oas1g STAT1. Total RNA mouse brain tissues extracted, reverse-transcribed, analyzed via qRT-PCR. Proteins extracted cells, quantified, separated SDS-PAGE, transferred PVDF membranes, probed antibodies. fixed, permeabilized, blocked, stained antibodies for STAT1, then visualized photographed. Bioinformatics machine revealed that gene, AUC 0.812. associated interferon-related pathways. Expression validated models, where it upregulated after microglial activation. Knockdown experiments suggested siOas1g attenuated effect siSTAT1, expressions STAT1 p-STAT1 elevated. could reverse indicating potentially regulates ISGs through pathway. We demonstrated ISG can downregulate activation IFN-β reducing expression neuroinflammation. might be beneficial candidate prevention treatment