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 carried out initial studies in the Parkinsonian Syndrome known as Progressive Supranuclear Palsy. These studies showed that there is significant increase in lipid peroxidation in the subthalamic nucleus. We developed a novel column switching assay for measurement of an oxidative marker of damage to DNA in human body fluids. We found that both overexpression of manganese superoxide dismutase, a major free radical scavenging enzyme, as well as Bc12 and a dominant negative inhibitor of interleukin converting enzyme all significantly attenuate NPTP induced dopaminergic neurotoxicity. This is accompanied by reductions in markers of oxidative stress. We also found that a number of therapeutic interventions, which may modulate oxidative stress, are effective in the NPTP model. We found that several novel free radical spin traps attenuate MPTP induced neurotoxicity and also attenuate%oxidative damage. Lastly, we found that oral administration of creatine or cyclocreatine are neuroprotective against MPTP neurotoxicity. The studies to date, have made significant progress on the original aims of the proposal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA376121
Entities
People
- Ann B. Young
- M. F. Beal
Organizations
- Massachusetts General Hospital