Disruptive strategies to understand the role(s) of reactive oxygen species in physiology and disease

Oxidative stress is an event associated with a variety of neurological disorders, including stroke. It occurs when neurons are unable to maintain reactive oxygen species (ROS) homeostasis. Clinical trials using chemical antioxidants targeting ROS to treat both ischemic and hemorrhagic stroke have thus far failed, suggesting ROS plays a complex role in cellular function. Researchers are interested in understanding specific cellular events that are associated with oxidative stress leading to neuronal death and have developed an in vitromodel using destabilization domains (dd; developed by Thomas Wandless at Stanford University) fused to known antioxidant enzymes to finely regulate their expression in cultured neurons. Using this model in cells under oxidative stress conditions, scientists can differentiate ROS-induced events that cause cell death from those that do not. This strategy will help in understanding the complex role of ROS in cellular function and potentially identify specific therapeutic targets that are involved in oxidative stress.