Role of Delta FosB in the Development of Levodopa-induced Dyskinesia

The goal of this project is to study mechanisms responsible for the dyskinesia side effect of levodopa seen in patients with Parkinson's disease. The proposed experiments focus on a protein, called FOSB, which accumulates in the striatum region of brain in pre-clinical models with a Parkinson's disease-like syndrome that have been treated repeatedly with levodopa. FOSB is interesting because it is a stable protein, which once induced persists in brain for a long period of time. Accordingly, FOSB could mediate dyskinesias long after the last levodopa treatment is given. In an international collaboration involving investigators at The University of Texas Southwestern Medical Center at Dallas and the Universite Victor Segalen in Bordeaux, France, our team will directly study the hypothesis that FOSB is one cause of levodopa-induced dyskinesia and that blockade of FOSB reduces the dyskinesias observed in our model. These experiments could have important impact on our understanding of the side effect of levodopa treatment and on our ability to reduce those side effects.