The Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation -- Innamorato et al. 181 (1): 680 -- The Journal of Immunology

The Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation -- Innamorato et al. 181 (1): 680 -- The Journal of Immunology: "Model proposed for modulation of microglia by the Nrf2/HO-1 axis. Pathogenic or neurotoxic insults (LPS) interact with pattern recognition receptors (TLR4) and trigger the early release of NADPH oxidase-mediated ROS and other proinflammatory factors. The increase of intracellular ROS is then detected by Nrf2, guardian of redox homeostasis, which activates a set of antioxidant and anti-xenobiotic genes, including HO-1. This late antioxidant response restores the redox balance, inhibits NADPH oxidase and down-regulates TLR4, driving active microglia back to the resting state. Genetic variability in key antioxidant enzymes, environmental alterations, or just the normal decline of redox homeostasis that occurs with aging leads to inefficient redox control and reduced capacity to down-modulate active microglia. This fact results in microglial activation and brain damage. Pharmacologic action on the Nrf2/HO-1 axis reinforces or restores microglial redox control, strengthens the negative loop, and assists in reduction of neuroinflammation."