SARS-CoV-2-Induced Type I Interferon Signaling Dysregulation in Olfactory Networks Implications for Alzheimer’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Concept Design
2.2. Dataset Selection
- Regarding study design:
- Reviews.
- Studies on children.
- In vitro or animal experiments, including gene expression data derived from such experiments.
- Study design unrelated to COVID-19 or focusing on a specific comorbidity.
- Sample size <5 per group.
- Regarding gene expression data:
- Gene expression data limited on SARS-CoV-2 entry factors.
- Gene expression data are limited on immune or other gene panels.
2.3. Leveraging Gene Set Enrichment Analysis (GSEA) Results from COVID-19 and Alzheimer’s Disease Datasets
2.4. Detection of Specific Overlapping Genes in Type I Interferon Signatures and Their Determination as Gene Network–the Minimal Dysregulated Network
2.5. Leveraging the Agora Multi-Omics Database to Identify Gene-Disease Associations with Alzheimer’s Disease
3. Results
3.1. Interferon Signaling Pathways Is Significantly Enriched along the Transolfactory Route in COVID-19 and in Response to Alzheimer’s Disease Pathology
3.2. Shared Genes between the Transolfactory Route and in Response to Alzheimer’s Disease Pathology Represent a Type I Interferon Network Containing IFITM and OAS Family Genes
3.3. Gene-Disease Associations between the Type I Interferon Signature and Alzheimer’s Disease Diagnosis
4. Discussion
4.1. Type I Interferon as a Mechanism for Cognitive Impairment in Long COVID
4.2. Type I Interferon Signaling as Common Ground between COVID-19 and Alzheimer’s Disease: A Hint towards Nucleic Acid Immunity and the cGAS-STING-IFITM3 Axis
4.3. Limitations, Strengths, and Outstanding Questions
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Reactome Term ID | Term Description | False Discovery Rate |
---|---|---|
R-HSA-909733 | Interferon alpha/beta signaling | 5.68 × 10−31 |
R-HSA-877300 | Interferon-gamma signaling | 1.51 × 10−8 |
R-HSA-1236977 | Endosomal/Vacuolar pathway | 8.23 × 10−8 |
R-HSA-1236974 | ER-Phagosome pathway | 1.40 × 10−6 |
R-HSA-983170 | Antigen Presentation: Folding, assembly, and peptide loading of class I MHC | 1.84 × 10−6 |
R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 4.65 × 10−6 |
R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 5.53 × 10−6 |
R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 5.74 × 10−5 |
R-HSA-2172127 | DAP12 interactions | 0.00049 |
R-HSA-1280218 | Adaptive Immune System | 0.00097 |
R-HSA-5663205 | Infectious disease | 0.0027 |
R-HSA-8983711 | OAS antiviral response | 0.0029 |
R-HSA-168249 | Innate Immune System | 0.005 |
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Vavougios, G.D.; Mavridis, T.; Doskas, T.; Papaggeli, O.; Foka, P.; Hadjigeorgiou, G. SARS-CoV-2-Induced Type I Interferon Signaling Dysregulation in Olfactory Networks Implications for Alzheimer’s Disease. Curr. Issues Mol. Biol. 2024, 46, 4565-4579. https://doi.org/10.3390/cimb46050277
Vavougios GD, Mavridis T, Doskas T, Papaggeli O, Foka P, Hadjigeorgiou G. SARS-CoV-2-Induced Type I Interferon Signaling Dysregulation in Olfactory Networks Implications for Alzheimer’s Disease. Current Issues in Molecular Biology. 2024; 46(5):4565-4579. https://doi.org/10.3390/cimb46050277
Chicago/Turabian StyleVavougios, George D., Theodoros Mavridis, Triantafyllos Doskas, Olga Papaggeli, Pelagia Foka, and Georgios Hadjigeorgiou. 2024. "SARS-CoV-2-Induced Type I Interferon Signaling Dysregulation in Olfactory Networks Implications for Alzheimer’s Disease" Current Issues in Molecular Biology 46, no. 5: 4565-4579. https://doi.org/10.3390/cimb46050277