Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB and Wnt/Catenin Pathway Signaling Underpin ME and chronic fatigue, 2021, Maes et al

Title
Aberrations in the Cross-Talks Among Redox, Nuclear Factor-κB and Wnt/Catenin Pathway Signaling Underpin Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: A Review and New Hypothesis Based on Results of Network, Enrichment and Annotation Analyses

Abstract
There is evidence that chronic fatigue spectrum disorders (CFAS-D) including Myalgic Encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue with physiosomatic symptoms including when due to comorbid medical disease are characterized by neuroimmune and neuro-oxidative biomarkers. The present study was performed to delineate the protein-protein interaction (PPI) network of CFAS-D and to discover the pathways, molecular patterns and domains enriched in their PPI network.

We performed network, enrichment and annotation analysis using differentially expressed proteins and metabolics, which we established in CFAS-D patients. PPI network analysis revealed that the backbone of the highly connective CFAS-D network comprises NFKB1, CTNNB1, ALB, peroxides, NOS2, TNF, and IL6, and that the network comprises interconnected immune-oxidative-nitrosative and Wnt/catenin subnetworks. MultiOmics enrichment analysis shows that the CFAS-D network is highly significantly associated with cellular (antioxidant) detoxification, hydrogen peroxide metabolic process, peroxidase and oxidoreductase activity, IL10 anti-inflammatory signaling, and neurodegenerative, canonical Wnt, the catenin complex, cadherin domains, cell-cell junctions and TLR2/4 pathways; and the transcription factors NF-κB and RELA.

The top-10 DOID annotations of the CFAS-D network include four intestinal, three immune system disorders, cancer and infectious disease. Custom GO term annotation analysis revealed that the CFAS-D network is associated with a response to a toxic substance, lipopolysaccharides, bacterium or virus.

In conclusion, CFAS-D may be triggered by a variety of stimuli and their effects are mediated by aberrations in the cross-talks between redox, NF-κB, and Wnt/catenin signaling pathways leading to dysfunctions in multicellular organismal homeostatic processes.

https://www.preprints.org/manuscript/202109.0201/v1

Posting mainly because one of the genetic mutations I have affects a cadherin that normally forms a complex with beta-catenin so it seems like it could be relevant to the process being described here.

 

That's a big claim in the title, hopefully the research lives up to it. Many of those components have appeared in me/cfs research over the years - IL-10 is one of the few cytokines that sticks out frequently enough to be a little curious about.

 

Now published at https://www.frontiersin.org/articles/10.3389/fpsyt.2022.822382/full

 

That is a complicated and jargon-heavy paper. It's using machine learning to pinpoint the hotspots relating to ME and the related disorders. The authors use the term "chronic fatigue spectrum disorders (CFAS-Ds)", in which they include myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS), and chronic fatigue (CF). I haven't worked out where the 'A' comes in - maybe 'associated'.

They also appear to define a new term "physiosomatic symptoms" as a pushback against "psychosomatic symptoms", which they argue are not psychogenic. Before reading their complicated findings and discussion, it's probably worth quoting their opening position statements, particularly given that this paper is in a psychiatry journal (my highlights).

They do then get a bit self-referential.

 

Those fly biologists are a funny bunch.

https://en.wikipedia.org/wiki/Hedgehog_signaling_pathway