APPA [AKL4] is an investigational NFkB and Nrf2 modulator.
NF-κB is a key intracellular messenger that plays a central role in inflammation through its ability to induce transcription of proinflammatory genes.
Nrf2 is a factor that regulates gene transcription of anti-oxidants in thereby reducing damage by the reactive oxidant species (ROS) generated during inflammation.
NF-κB and Nrf2 activity is essential for maintaining coordinated cellular responses to resolve the inflammatory status of the cell/tissue.
In chronic pathologic states such as OA where there is an imbalance between the Nrf2 and NF-κB pathways a robust but fine-tuned NF-κB and Nrf2 response is essential for an appropriate inflammatory response and subsequent resolution.
By regulating the cross-talk between Nrf2 and NF-κB, APPA regulates rather than blocks the immune response without significantly affecting neutrophil host defence mechanisms.