Role of Heme Oxygenase 2 Interactors in AD Models

Project Summary

The onset and progression of Alzheimer's disease (AD) can be quite varied. To date, it is very difficult to predict an individual's risk or even to detect the preliminary signs of the condition before dementia appears. Dr. Dore has been studying the neuronal form of a protein called heme oxygenase (HO2), which may play a pivotal role in AD. It is already believed that oxidative stress plays a role in AD, and that certain types of highly reactive oxygen species (ROS) cause cellular damage. The control of the production and excretion of these molecules is necessary to prevent cellular damage and is maintained by antioxidants. HO2 has antioxidant properties and also binds to amyloid precursor protein (APP). Furthermore, an essential component for HO2 activity is cytochrome P450 reductase (CPR) and CPR is a key element in generating ROS. Dr. Dore hypothesizes that CPR, in conjunction with HO2, regulates the generation of ROS and is important in AD. The objective of this research is to characterize the interactions between APP and HO2 using cell culture systems and transgenic mouse models. New mouse models lacking HO2 will be bred, and it is expected that significantly more plaques will be apparent in mice with HO2 deletions compared to normal mice. Dr. Dore will also examine the contribution of CPR in the ROS damage associated with AD. He believes that a better understanding of the interactions between APP, HO2 and CPR will help elucidate the contribution of neuronal oxidant stress damage and its role in AD.