Our goal is to develop novel therapeutic agents for the treatment of Parkinson's disease. We will focus on two compounds. One of these blocks the mitochondrial permeability transition (MPT), which is implicated in both necrotic and apoptotic cell death. The other compound, which we will examine is a triterpenoid which activates the Nrf2/ARE pathway. This pathway upregulates a large number of genes involved in antioxidant defenses and it downregulates genes involved in inflammation.
Since both oxidative damage and inflammation are implicated in PD pathogenesis, a compound that can modulate both pathways holds great promise as a potential therapeutic agent for slowing the progression of Parkinson's disease.
Dr. Beal tested whether novel antioxidant compounds (tetrapeptides and triterpenoids) were protective in MPTP mice. Both sets of compounds showed some protection when given concomitant to MPTP toxin treatment.