期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/ijms22137150
关键词
ALS; blood; co-expression networks; neurodegeneration; switch genes; sex differences
资金
- National Institute on Aging (NIA) [R01AG062176]
This study identified switch genes associated with drastic transcriptomic changes in ALS patients' blood, revealing potential sex-specific roles in the disease mechanism, with males showing metabolic pathway enrichment and females related to infectious diseases and inflammation.
Understanding the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is a major challenge. We used co-expression networks implemented by the SWitch Miner software to identify switch genes associated with drastic transcriptomic changes in the blood of ALS patients. Functional analyses revealed that switch genes were enriched in pathways related to the cell cycle, hepatitis C, and small cell lung cancer. Analysis of switch genes by sex revealed that switch genes from males were associated with metabolic pathways, including PI3K-AKT, sphingolipid, carbon metabolism, FOXO, and AMPK signaling. In contrast, female switch genes related to infectious diseases, inflammation, apoptosis, and atherosclerosis. Furthermore, eight switch genes showed sex-specific gene expression patterns. Collectively, we identified essential genes and pathways that may explain sex differences observed in ALS. Future studies investigating the potential role of these genes in driving disease disparities between males and females with ALS are warranted.
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