Nrf2 as a Therapeutic Target for Stroke and Neurodegeneration

Stroke is a leading cause of death and disability inNorth America. One major cause of nerve tissue damage during strokeis the accumulation of reactive oxygen species- moleculesthat steal electrons from healthy cells in a process known asoxidation. This thesis describes a novel approach to increaseantioxidant levels in order to maintain oxidative balance and preventcellular damage during stroke. The stress-responsive transcriptionfactor Nrf2 is able to launch the endogenous mechanisms of cellulardefense and repair. Nrf2 represents a master switch thatcoordinates tens to hundreds of antioxidant and detoxification genesworking in synergy. In rodent models of stroke andneurodegeneration increased Nrf2 activity was found to promote neuronalsurvival and improve recovery of limb function weeks to monthsfollowing injury. Interestingly a number of molecules that activateNrf2 are found in cruciferous vegetables such as broccoli sproutssuggesting the possibility of practical diet-based therapies.