STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive–Compulsive Disorder

Abstract

Background: There are no data available on the levels of genetic networks between obsessive–compulsive disorder (OCD) and multiple sclerosis (MS). To this point, we aimed to investigate common mechanisms and pathways using bioinformatics approaches to find novel genes that may be involved in the pathogenesis of OCD in MS. Methods: To obtain gene–gene interactions for MS and OCD, the STRING database was used. Cytoscape was then used to reconstruct and visualize graphs. Then, ToppGene and Enrichr were used to identify the main pathological processes and pathways involved in MS-OCD novel genes. Additionally, to predict transcription factors and microRNAs (miRNAs), the Enrichr database and miRDB database were used, respectively. Results: Our bioinformatics analysis showed that the signal transducer and the activator of transcription 3 (STAT3) and neurotrophic receptor tyrosine kinase 2 (NTRK2) genes had connections with 32 shared genes between MS and OCD. Furthermore, STAT3 and NTRK2 had the greatest enrichment parameters (i.e., molecular function, cellular components, and signaling pathways) among ten hub genes. Conclusions: To summarize, data from our bioinformatics analysis showed that there was a significant overlap in the genetic components of MS and OCD. The findings from this study make two contributions to future studies. First, predicted mechanisms related to STAT3 and NTRK2 in the context of MS and OCD can be investigated for pharmacological interventions. Second, predicted miRNAs related to STAT3 and NTRK2 can be tested as biomarkers in MS with OCD comorbidity. However, our study involved bioinformatics research; therefore, considerable experimental work (e.g., postmortem studies, case–control studies, and cohort studies) will need to be conducted to determine the etiology of OCD in MS from a mechanistic view.

Choroid plexus enlargement in acute neuroinflammation is tightly interrelated to the tyrosine receptor signalling

“…Furthermore, it can bind NTF4/neurotrophin-4 and NTF3/neurotrophin-3, which regulates neuron survival. A recent genetic study, detected that the NTRK2 gene (of note, together with the STAT3 gene) has a significant overlap in the genetic susceptibility of MS and linked psychiatric comorbidity ( 18 ). In their paper, the NTRK2 gene had the highest enrichment and participated in the main signalling pathways (i.e.…”

Obsessive–compulsive symptoms and brain lesions compatible with multiple sclerosis

“…OCS in MS/RIS may be associated with a genetic predisposition, mild neuroinflammatory processes, strategic MS lesions and frontotemporal volume loss, or neurotransmitter alterations. Recently, a significant overlap in the genetic components ( STAT3 and NTRK2 ) of OCD and MS has been described (Sepehrinezhad et al 2022 ). Mild neuroinflammatory processes (e.g., T-cell dysfunction or cytokine changes) are rarely investigated but cannot be excluded (Bechter 2020 ; Endres et al 2022 ).…”

New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets

“… 12 Afterward, a TSV file was downloaded and uploaded into Cytoscape version 3.7.0 to visualize the genetic network and analyzed main network parameters such as degree and betweenness centrality. 13 - 15 Top genes with more degree and greater betweenness centrality were considered as hub genes. 16 …”