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Protection by Purines in Toxin Models of Parkinson's Disease

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Technical Report,17 Jan 2014,13 Jul 2015

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Massachusetts General Hospital Boston

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During the current reporting period we have made further progress toward our main purpose of characterizing the mechanisms and neuroprotective potential of purines linked to better outcomes in Parkinsons disease. We have made significant progress toward the original SAs with the systematic characterization of the astrocytic Nrf2 antioxidant pathway as a potential specific mechanism of urate neuroprotection, as well as further development of mouse models for characterizing the urate neurobiology in models of PD. The project has also facilitated collaborative advances in in synculein and urate biomarker discovery for PD. The results to date provide a solid foundation on which to build our subsequent experiments of the project. In the past year they have also had a major impact in directly supporting the development of a novel urate-elevating neuroprotective strategy, and its advance to phase 3 clinical efficacy testing in a major randomized clinical trial. Together our findings strengthen the rationale for pursuing purine targets as candidate neuroprotective strategies for PD, and have epidemiological and military, as well as translational significance.

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