Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine. Relevance to Parkinsonʼs disease

THE mechanism of nigral cell death in Parkinson's disease (PD) remains unknown, but it is increasingly proposed that free radical reactions are important in the disease pathology. One of the most striking features of PD is an approximate 40% decrease in the levels of reduced glutathione (GSH) which occurs early in the development of the disease. We describe a possible mechanism of GSH depletion which results from the reaction of L-DOPA and dopamine with the superoxide free radical (O2-) and leads to a very rapid loss of GSH.