Bioinformatics analysis of the alterations in neuregulin 1/4 and their correlation with ferroptosis-related genes in amyotrophic lateral sclerosis

Abstract

Background & Objective: Dysregulation of the ErbB4 signaling pathway has been implicated as a significant factor in the pathogenesis of amyotrophic lateral sclerosis （ALS）, with neuregulin 1 (NRG1) and NRG4 serving as key regulatory ligands of ErbB4. This study mainly employs bioinformatics approaches to investigate the association between changes in ferroptosis-related genes and NRG1/4 in ALS.

Methods: Differentially expressed genes (DEGs) in ALS spinal cord tissue were identified from the GEO database, with a focus on ferroptosis-related genes sourced from FerrDb. Subsequent protein-protein interaction (PPI) network was constructed using Cytoscape software. The expression levels of NRG1 and NRG4 in ALS were then examined, followed by a correlation analysis between these genes and main ferroptosis-related DEGs in ALS.

Result: In the anterior horn tissue, 6 ferroptosis-related genes were downregulated and 3 were upregulated, whereas in motor neurons, 11 ferroptosis-related genes were upregulated and 8 were downregulated. In normal anterior horn tissues, NRG4 exhibits a positive correlation with MAP3K14, whereas in anterior horn tissues of ALS patients, it is positively correlated with PANX2. In motor neurons, NRG1 was negatively correlated with JUN, SLC7A11, and PANX2 in ALS. Additionally, NRG4 was negatively correlated with TIMP1, SOX2, and AR in normal controls, and with CFL1 and JUN in ALS. PANX2 showed a positive correlation with both NRG1 and NRG4 in both normal controls and ALS patients.

Conclusion: The bioinformatics analysis results underscore the potential of NRG1/4 signaling in mitigating ALS by regulating specific ferroptosis-related genes.