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Abstract:
Parkinson's disease is characterized by the depletion of glutathione (GSH) in, the substantia nigra and the degeneration of nigral dopamine neurons. In our stud: we examined the relationship between cellular GSH depletion and neuronal degeneration. Using rat mesencephalic cultures as a model, we found that GSH depletion results in phospholipase A, (PLA(sub 2))-dependent release of arachidonic acid and increase in lipoxygenase (LOX-dependent arachidonic acid metabolism. These events generate reactive oxygen species, which accumulate in the cells and result in oxidative stress and cell death. Cell death can be prevented by interrupting different steps of this process, including replenishment of GSH, inhibition of PLA_ activity, inhibition of LOX activity and increase in the antioxidant defenses of the cells (up-regulation of superoxide dismutase, addition of ascorbic acid). Our studies provide information, which may be important in the understanding of the etiology of Parkinson's disease and could offer insights for the design of medication to prevent the progress of the disorder in Parkinson's patients.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Final rept. 1 Jul 1999 - 1 Jul 2003 |
| Pages: |
65 |
| Report Date: |
AUG 2003 |
| Contract Number: |
DAMD179919557 |
| Report Number: |
A032264 |
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