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Pre-Clinical Testing of New Hydroxybutyrate Analogues
Final rept. 1 Jul 2010-30 Jun 2011
COLUMBIA UNIV NEW YORK
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Mitochondria are the powerplants of the cell. They produce the ATP necessary for the neuronsto engage in reactions geared toward their proper function. Mitochondria contain a series of enzymes, in a chain-like array, that pass electrons along this chain via proton motive force which is initiated by complex I, the first of this series of enzymes. Complex I deficiency isconsidered one of the hallmarks of Parkinson s Disease as it contributes greatly to the energy crisis in the neurons. In an earlier study, bypassing this complex I deficiency using D- - hydroxybutyrate D HB in the MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of PD, dopamine neurons in the substantia nigra pars compacta were protected. Our goal in this study is to assess the effects of D HB analogues to ascertain if they are longer-acting compounds than the parent compound. Although obtaining the first and only drug at the moment was quite difficult it took close to 10 months, we have now initiated our first experiment which is to determine the effective dose to use in future experiments.
APPROVED FOR PUBLIC RELEASE