Andy Yi-an Shih

Nrf2 As a Therapeutic Target for Stroke and Neurodegeneration Andy Yi-an Shih

Stroke is a leading cause of death and disability in North America. One major cause of nerve tissue damage during stroke is the accumulation of reactive oxygen species- molecules that steal electrons from healthy cells in a process known as oxidation. This thesis describes a novel approach to increase antioxidant levels in order to maintain oxidative balance and prevent cellular damage during stroke. The stress-responsive transcription factor, Nrf2, is able to launch the endogenous mechanisms of cellular defense and repair. Nrf2 represents a master switch that coordinates tens to hundreds of antioxidant and detoxification genes working in synergy. In rodent models of stroke and neurodegeneration, increased Nrf2 activity was found to promote neuronal survival and improve recovery of limb function weeks to months following injury. Interestingly, a number of molecules that activate Nrf2 are found in cruciferous vegetables, such as broccoli sprouts, suggesting the possibility of practical diet-based therapies.