Cross-Talking Pathways of Rapidly Accelerated Fibrosarcoma-1 (RAF-1) in Alzheimer's Disease.

Alzheimer's disease (AD) becomes one of the main global burden diseases with the aging population. This study was to investigate the potential molecular mechanisms of rapidly accelerated fibrosarcoma-1 (RAF-1) in AD through bioinformatics analysis. Differential gene expression analysis was performed in GSE132903 dataset. We used weight gene correlation network analysis (WGCNA) to evaluate the relations among co-expression modules and construct global regulatory network. Cross-talking pathways of RAF-1 in AD were identified by functional enrichment analysis. Totally, 2700 differentially expressed genes (DEGs) were selected between AD versus non-dementia control and RAF-1-high versus low group. Among them, DEGs in turquoise module strongly associated with AD and high expression of RAF-1 were enriched in vascular endothelial growth factor (VEGF), neurotrophin, mitogen-activated protein kinase (MAPK) signaling pathway, oxidative phosphorylation, GABAergic synapse, and axon guidance. Moreover, cross-talking pathways of RAF-1, including MAPK, VEGF, neurotrophin signaling pathways, and axon guidance, were identified by global regulatory network. The performance evaluation of AUC was 84.2%. The gene set enrichment analysis (GSEA) indicated that oxidative phosphorylation and synapse-related biological processes were enriched in RAF-1-high and AD group. Our findings strengthened the potential roles of high RAF-1 level in AD pathogenesis, which were mediated by MAPK, VEGF, neurotrophin signaling pathways, and axon guidance.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)