NRTS As Treatment in Parkinsons Disease

Oxygen free radicals and oxidative damage have been shown to be involved in neurodegenerativediseases including Parkinson's Disease. The PI has discovered that certain nitrone-based free radicaltraps (NRTs), which react with and trap free radicals, protect experimental animals from an experimentalmodel of Parkinson's Disease, the MPTP (l-methyl-4-phenyl-1, 2, 5, 6-tetrahydropyridine)- induced lossof caudate dopamine in C57BL/6 mice. They have also discovered that MPTP induces increasedhydroxyl free radical formation in treated mice. The goal of Phase I is to determine if NRTs protect inexperimental models of Parkinson's Disease. The specific aims are: (1) to determine if, duringMPTP-induced Parkinson's Disease, the tissue is injured by oxidative damage; (2) to determine theeffectiveness of a series of NRTs in preventing brain damage as assessed by dopamine caudate loss anddetermine if NRTs protect by reacting with either the primary reactive oxygen species (ROS) or theirsecondary reaction products and thus prevent the oxidative cascade of events which leads to tissueinjury; and (3) to synthesize and test NRTs that have potential effectiveness in treating Parkinson'sDisease patients.