Fig. 2.

Activation of the Keap1/Nrf2/ARE/pathway by the SOs is cytoprotective. Nrf2 has been described previously (Lee et al., 2005) as a “multiorgan protector,” because this system can protect against diseases in a number of organs, including the brain, lungs, kidney, heart, liver, and eye. The SOs are among the most potent known inducers of the Nrf2 pathway, and these drugs not only activate Nrf2 in all of these organs but also protect the organs against a variety of diseases driven by inflammatory or oxidative stress. SOs that cross the blood-brain barrier are beneficial in experimental models of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and ALS. These drugs also reduce damage to the eye from light, uveitis, or ischemia reperfusion and reduce cardiomyopathy induced by smoking and reduce the disease process in the lung in animal models of COPD, emphysema, asthma, and ALI/ARDS. In the liver and kidney, the SOs protect against toxicity from insults such as aflatoxin, ConA, acetaminophen, or cisplatin and against injury from ischemia reperfusion.