Oxidative Stress and Parkinson's Disease a

The underlying mechanism of cell death in substantia nigra of Parkinson's disease patients remains unknown. Biochemical changes occurring in substantia nigra in Parkinson's disease (increased iron levels, inhibition of complex I activity and decreased reduced glutathione levels; GSH) suggest that oxidative stress and free radical species may be involved. In particular, a decrease in GSH levels may be an early component of the process, since this also occurs in incidental Lewy body disease (presymptomatic Parkinson's disease). GSH is lost only from the substantia nigra in Parkinson's disease and this does not occur in other neurodegenerative disorders of the basal ganglia. GSH loss appears to be global throughout the substantia nigra and not localized to either the glia or neuronal elements. The activity of enzymes involved in the glutathione cycle are normal with the exception of gamma-glutamyltranspeptidase, the activity of which is increased. This could result in increased removal and degradation of glutathione from cells. Depletion of GSH in rat using L-buthionine-[S, R]-sulfoxamine (BSO) potentiates 6-hydroxydopamine (6-OHDA) toxicity but does not in itself produce degeneration of the nigrostriatal pathway. Oxidative stress may be a potentially important factor in the degeneration of the substantia nigra in Parkinson's disease and warrants further investigation into its role in this process.

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