Nrf2 and NF-κB are two key transcription factors regulating cellular responses to oxidative stress and inflammation. They interact through complex molecular mechanisms, with Nrf2 promoting antioxidant responses and NF-κB driving inflammatory responses. The absence of Nrf2 can exacerbate NF-κB activity, increasing cytokine production, while NF-κB can modulate Nrf2 transcription and activity. Nrf2 is regulated by Keap1, which mediates its ubiquitination and degradation. Oxidative stress can modify Keap1, leading to Nrf2 nuclear accumulation. Nrf2 binds to AREs and activates antioxidant genes. NF-κB is regulated by IκBα, which is phosphorylated and degraded, allowing NF-κB to translocate to the nucleus. NF-κB can also enhance mitochondrial activity and NADPH oxidase expression, contributing to reactive oxygen species (ROS) production. The interplay between Nrf2 and NF-κB is crucial for maintaining cellular homeostasis and preventing diseases such as neurodegeneration, autoimmune disorders, and cancer. Nrf2 activation by phytochemicals like sulforaphane and CDDO-Im can reduce inflammation and protect against oxidative stress. p65, a component of NF-κB, can inhibit Nrf2 by competing for CBP and promoting histone deacetylation. The balance between these pathways is essential for cellular function, and their dysregulation is linked to various diseases. Targeting Nrf2 and NF-κB pathways offers potential therapeutic strategies for neurodegenerative diseases. Understanding their interactions is key to developing effective treatments.Nrf2 and NF-κB are two key transcription factors regulating cellular responses to oxidative stress and inflammation. They interact through complex molecular mechanisms, with Nrf2 promoting antioxidant responses and NF-κB driving inflammatory responses. The absence of Nrf2 can exacerbate NF-κB activity, increasing cytokine production, while NF-κB can modulate Nrf2 transcription and activity. Nrf2 is regulated by Keap1, which mediates its ubiquitination and degradation. Oxidative stress can modify Keap1, leading to Nrf2 nuclear accumulation. Nrf2 binds to AREs and activates antioxidant genes. NF-κB is regulated by IκBα, which is phosphorylated and degraded, allowing NF-κB to translocate to the nucleus. NF-κB can also enhance mitochondrial activity and NADPH oxidase expression, contributing to reactive oxygen species (ROS) production. The interplay between Nrf2 and NF-κB is crucial for maintaining cellular homeostasis and preventing diseases such as neurodegeneration, autoimmune disorders, and cancer. Nrf2 activation by phytochemicals like sulforaphane and CDDO-Im can reduce inflammation and protect against oxidative stress. p65, a component of NF-κB, can inhibit Nrf2 by competing for CBP and promoting histone deacetylation. The balance between these pathways is essential for cellular function, and their dysregulation is linked to various diseases. Targeting Nrf2 and NF-κB pathways offers potential therapeutic strategies for neurodegenerative diseases. Understanding their interactions is key to developing effective treatments.