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Protection by Purines in Toxin Models of Parkinson's Disease
Technical Report,17 Jan 2011,14 Jul 2015
Massachusetts General Hospital Boston United States
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During the reporting period we have made substantial progress toward our main purpose of characterizing the mechanisms and neuroprotective potential of purines adenosine, caffeine, and urate -- linked to better outcomes in Parkinsons disease PD, and toward all three of the original Specific Ams SAs. Major accomplishments included a definitive demonstration that caffeines neuroprotective effect in a toxin model of PD requires the adenosine A2A receptor, and conversely that a transgenic alpha-synuclein model of PD also requires the A2A receptor SA 1. We also discovered that a mutation in the gene encoding the urate-metabolizing enzyme urate oxidase UOx raised brain levels of urate and protected mice in another toxin model of PD, supporting the neuroprotective potential of targeting urate elevation in PD SA 2.
APPROVED FOR PUBLIC RELEASE