Understanding How NF-κB Pathway Impacts COVID-19 Severity and Inflammation

What is it about?

This article explores the critical role of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in the inflammatory response associated with COVID-19. It conducts a comprehensive computational reanalysis and literature review focusing on SARS-CoV-2 entry mechanisms, toll-like receptor (TLR) signaling, and NF-κB activation pathways. The study highlights how SARS-CoV-2 facilitates viral entry through ACE2 receptors and TMPRSS2 activity, which in turn activates TLRs, leading to NF-κB pathway activation and cytokine production. It emphasizes the crosstalk between NF-κB and other signaling pathways, such as JAK/STAT and NLRP3 inflammasome, which exacerbate the cytokine storm and lung injury in severe COVID-19 cases. The article also discusses potential therapeutic strategies targeting NF-κB, including corticosteroids and repurposed drugs like dexamethasone, which have shown promise in reducing inflammation. The findings underscore NF-κB's pivotal role in COVID-19 pathogenesis and suggest that targeting this pathway could lead to improved clinical outcomes.

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Why is it important?

This review examines the critical role of the NF-κB signaling pathway in the pathogenesis of COVID-19, highlighting its contribution to the hyperinflammatory response associated with severe disease outcomes. By synthesizing existing literature, the review underscores the potential of targeting NF-κB signaling as a therapeutic strategy to mitigate the cytokine storm and improve clinical outcomes in COVID-19 patients. This synthesis is significant due to the ongoing need to understand the molecular mechanisms driving severe COVID-19 and to develop effective treatments. Key Takeaways: 1. The review summarizes that SARS-CoV-2 entry into host cells through ACE2 receptors triggers immune signaling cascades, particularly via toll-like receptors (TLRs), leading to activation of both canonical and noncanonical NF-κB pathways, which play a pivotal role in the inflammatory response. 2. It highlights the extensive crosstalk between NF-κB and other immune regulatory pathways such as the JAK/STAT axis and NLRP3 inflammasome, which amplifies the cytokine storm and contributes to severe disease manifestations like acute respiratory distress syndrome (ARDS). 3. The review discusses potential therapeutic strategies targeting NF-κB signaling, including the use of corticosteroids, IKK inhibitors, and repurposed drugs like dexamethasone and resveratrol, which have shown promise in reducing NF-κB-mediated inflammation and improving patient outcomes.