Oxidative Damage in Parkinson's Disease
Annual rept. 1 Oct 2000-30 Sep 2001
CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
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The objective of the present research is to determine whether there is a coherent body of evidence implicating oxidative damage in the pathogenesis of Parkinsons Disease and the MPTP model of Parkinsonism. In the past year, we have developed a novel column switching assay for measurement of oxidative damage to DNA in human body fluids. We have applied to this plasma samples of Parkinsons Disease patients. We have also developed a novel technique for directly looking for mitochondrial DNA mutations in isolated neurons of the substantia nigra of human postmortem brain. We have validated this methodology. We have found a relatively high mutation rate and control samples and intend to apply this to Parkinsons Disease. We have continued our studies to determine whether oxidative damage plays a critical role in MPTP toxicity. We have found that mice which are deficient in manganese superoxide dismutase show increased sensitivity to MPTP toxicity, which is accompanied by increases in free radical production. We also found that transgenic mice with a mutation associated with familial ALS showed increased sensitivity to MPTP toxicity. These mice are known to have increases oxidative damage. These studies have, therefore, made significant progress on the original aims of the proposal.
- Medicine and Medical Research