Nrf2/Keap1 Signaling Axis in the Brain: Master Regulator of Oxidative Stress in Neurodegenerative and Psychiatric Disorders

Abstract

The Nrf2/Keap1 signaling axis defends against oxidative damage by regulating antioxidant and cytoprotective genes. Beyond antioxidant function, Nrf2 influences neurogenesis, synaptic plasticity, mitochondrial bioenergetics, and glial-neuronal interactions. Dysregulation contributes to Alzheimer's, Parkinson's, Huntington's, ALS, and psychiatric disorders.

Key Findings

• NRF2/KEAP1 is master regulator of oxidative stress defense in the brain
• NRF2 influences neurogenesis, synaptic plasticity, mitochondrial function
• NRF2 dysregulation implicated in both neurodegenerative and psychiatric disorders
• Therapeutic strategies include natural/synthetic activators and gene therapy

Clinical Significance

Citation

Goel, F. et al. (2025). Nrf2/Keap1 in the Brain. Molecular Neurobiology.