Protein Kinase R–NF-kappaB Pathway

The Protein kinase R (PKR)–NF-kappaB pathway is a signaling axis that links the cellular stress sensor PKR to the activation of the transcription factor NF-κB. This pathway plays a crucial role in regulating immune responses, inflammation, apoptosis, and cell survival in response to various stresses, including viral infection and DNA damage. PKR is activated by dsRNA or other stressors, leading to phosphorylation events and subsequent activation of NF-κB through IκBα degradation. The pathway influences canonical NF-κB activation and can contribute to antiviral defense, inflammatory responses, tumor suppression, and cancer therapy resistance. Dysregulation is implicated in chronic inflammation, cancer, autoimmune diseases, and neurodegenerative disorders.

Inhibition of PKR activation; inhibition of NF-κB activation; modulation of downstream signaling pathways involved in inflammation, apoptosis, and cell survival