Oxidative Damage in Parkinson's Disease
Abstract
The overall goal of the proposal was to provide a detailed assessment of the role of oxidative damage in Parkinson's Disease (PD) postmortem brain tissue, body fluids of PD patients and in the MPTP model. There were trends towards increased oxidative damage markers in post mortem brain tissue of PD patients and a number of specific genes linked to oxidative stress were reduced in expression. There was increased lipid peroxidation in progressive supranuclear palsy brains. There were no significant alterations in 8-hydroxy-2- deoxyguanosine in the plasma of PD patients. We found that overexpression of manganese superoxide dismutase attenuated MPTP toxicity whereas its deficiency exacerbated detoxicity. Similarly, a deficiency of glutathione peroxidase exacerbated MPTP neurotoxicity. Overexpression of Bcl2 or a dominant-negative mutant of interleukin-l converting enzymes significantly attenuated MPTP toxicity. We found increases in oxidative damage markers in the substantia nigra of MPTP treated baboons. A number of free radical spintraps as well as a selective inhibitor of neuronal nitric oxide synthase protected against MPTP neurotoxicity. In summary, our studies showed further evidence linking oxidative damage to dopaminergic neurons in the substantia nigra as well as in the MPTP model of PD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2003
- Accession Number
- ADA423990
Entities
People
- M. F. Beal
Organizations
- Cornell University