Oxidative Damage in Parkinson's Disease
Abstract
The objective of the present research is to determine whether there is a coherent body of evidence implicating oxidative damage in the pathogenesis of Parkinson's Disease and the MPTP model of Parkinsonism. We found that there are significant decreases in alpha-ketoglutarate dehydrogenase complex and a significant increase in tissue malondialdehyde levels in the superior frontal cortex, the Parkinsonian syndrome known as Progressive Supranuclear Palsy. We are continuing studies looking at in situ hybridization probes for free radical enzymes. We have developed a novel column-switching assay for measurement of the oxidative marker of DNA damage in human body fluids. We have recently applied this to ALS patients and have found significant increases. We have also developed a novel assay for nitrogamma tocopherol, a marker for oxidative damage mediated by peroxynitrite. We are presently collecting samples from Parkinson's Disease patients to carry out measurements. We have continued our studies showing that oxidative damage plays a critical role in MPTP toxicity. We found that mice, which were deficient in cellular glutathione peroxidase, showed increased sensitivity to MPTP toxicity, which was accompanied by increases in free radical production. We also demonstrated that administration of MPTP to primates results in increased alpha-synuclein in the substantia nigra. These studies have, therefore, made significant progress on the original aims of the proposal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA418896
Entities
People
- M. F. Beal
Organizations
- Cornell University