Rps27a might act as a controller of microglia activation in triggering neurodegenerative diseases

Abstract

Neurodegenerative diseases (NDDs) are increasing serious menaces to human health in the recent years. Despite exhibiting different clinical phenotypes and selective neuronal loss, there are certain common features in these disorders, suggesting the presence of commonly dysregulated pathways. Identifying causal genes and dysregulated pathways can be helpful in providing effective treatment in these diseases. Interestingly, in spite of the considerable researches on NDDs, to the best of our knowledge, no dysregulated genes and/or pathways were reported in common across all the major NDDs so far. In this study, for the first time, we have applied the three-way interaction model, as an approach to unravel sophisticated gene interactions, to trace switch genes and significant pathways that are involved in six major NDDs. Subsequently, a gene regulatory network was constructed to investigate the regulatory communication of statistically significant triplets. Finally, KEGG pathway enrichment analysis was applied to find possible common pathways. Because of the central role of neuroinflammation and immune system responses in both pathogenic and protective mechanisms in the NDDs, we focused on immune genes in this study. Our results suggest that "cytokine-cytokine receptor interaction" pathway is enriched in all of the studied NDDs, while "osteoclast differentiation" and "natural killer cell mediated cytotoxicity" pathways are enriched in five of the NDDs each. The results of this study indicate that three pathways that include "osteoclast differentiation", "natural killer cell mediated cytotoxicity" and "cytokine-cytokine receptor interaction" are common in five, five and six NDDs, respectively. Additionally, our analysis showed that Rps27a as a switch gene, together with the gene pair { Il-18 , Cx3cl1 } form a statistically significant and biologically relevant triplet in the major NDDs. More specifically, we suggested that Cx3cl1 might act as a potential upstream regulator of Il-18 in microglia activation, and in turn, might be controlled with Rps27a in triggering NDDs.

Novel Insight Into the Role of Immune Dysregulation in Amyotrophic Lateral Sclerosis Based on Bioinformatic Analysis

“…The most highly enriched pathway in the turquoise module was cytokinecytokine receptor interaction, which regulates cytokine binding. This pathway is regarded as a crucial aspect of inflammation and is enriched in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease, multiple sclerosis, and schizophrenia (Guo et al, 2014;Sattlecker et al, 2016;Xu et al, 2016;Khayer et al, 2020). Notably, Ras, MAPK, and PI3K/AKT signaling were among the top enriched pathways in the pink module.…”

Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness

“…The successful identification of the switch genes in diseases can be consequential because they can be regarded as potential drug targets. In the meantime, switching genes can be helpful in decoding biological complexities 21 , 22 .…”

Identification of Potential Blood-based Biomarkers for Multiple Sclerosis

“…It was upregulated in GSE17048 and GSE21942. A study shows that RPS27A may be involved in controlling microglia activation and linked to the onset of neurodegenerative diseases [26]. Like RPS27A, the ribosomal protein gene RPS15A was also identified as a hub gene because it had a node degree of 11.…”