Grant: Project Grant

Parkinson's disease (PD) is the second most common neurodegenerative disease affecting as many as 10 million individuals worldwide. While aging is the greatest risk factor for PD, the role of aging in the disease is poorly understood. In the inherited forms of PD, the disease-causing mutations are present from birth and yet disease onset occurs multiple decades later. This indicates that these mutations are well-tolerated in younger individuals. Based on this observation, we wondered whether changes that take place during normal aging contribute to the development of PD. If so, then delaying some of these changes may be beneficial in PD. To test this idea, we used a simple model organism, the worm C. elegans, which has been used extensively to identify genes that modulate aging. We treated worm models of PD with genes that have been previously shown to increase lifespan, and measured the extent to which these genes could prevent the loss of brain cells. We found that all five aging-associated genes that we tested protected the brain cells from death and preserved their function. This experiment provides support for our idea that delaying changes that take place during aging will be beneficial in treating PD. The current proposal will build upon these exciting preliminary studies to answer two important questions: (1) Which genes that have been shown to influence aging will be the most beneficial in the treatment of PD?; and (2) How do these genes protect against PD? Importantly, these studies will serve to prioritize therapeutic targets to be validated in mammalian models in subsequent studies. This work has the potential to improve human health through the identification of novel therapeutic targets for the treatment of PD.