Nuclear factor-κB as a key inflammatory mediator in psychiatric diseases: A narrative review

Nuclear factor-κB (NF-κB) is a central transcription factor that links peripheral immune activation to neuroinflammatory responses in the brain, playing a key role in the pathophysiology of several psychiatric disorders. This review examines the aberrant activation of NF-κB in major depressive disorders, schizophrenia, post-traumatic stress disorder, bipolar disorder, and autism spectrum disorder. It delves into the cell-type-specific mechanisms through which NF-κB modulates neuroinflammation, synaptic plasticity, and neuronal function in microglia, astrocytes, and neurons, and explore its interactions with other key pathways, such as nuclear factor erythroid 2-related factor 2, hypoxia-inducible factor 1-alpha, and NOD-like receptor family pyrin domain containing 3. Furthermore, we summarize current indirect and direct therapeutic strategies targeting NF-κB signaling and discuss the potential of biomarker-guided personalized medicine.