Pre-Clinical Testing of New Hydroxybutyrate Analogues.

摘要

Mitochondria are the powerplants of the cell. They produce the ATP necessary for the neurons to 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 is considered 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.