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Abstract
Amino acid analysis of autopsied human brain showed reduced glutathione (GSH) content
significantly lower in the substantia nigra than in other brain regions. GSH was virtually
absent in the nigra of patients with Parkinson's disease. Oxidative degradation of
L-DOPA and dopamine in vivo may generate reactive oxygen species (hydrogen peroxide,
superoxide, hydroxyl radical, or singlet oxygen) which can damage membranes and other
cellular components. Since GSH is an important natural antioxidant, a deficiency of
GSH in the substantia nigra could make this region vulnerable to oxidative injury.
If confirmed, the hypothesis that loss of nigrostriatal dopaminergic neurons results
from a regional GSH deficiency could have important therapeutic implications for the
management and prevention of Parkinson's disease.