Nigral glutathione deficiency is not specific for idiopathic Parkinson's disease

The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. To establish whether a nigral glutathione deficiency is unique to PD, as is generally assumed, or is present in other Parkinsonian conditions associated with nigral damage, we compared levels of reduced glutathione (GSH) in postmortem brain of patients with PD to those with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). As compared with the controls, nigral GSH levels were decreased in the PD and PSP patient groups (P < 0.05 for PD [-30%], PSP [-21%]), whereas a similar decrease in the MSA patient group did not reach statistical significance (P = 0.078, MSA [-20%]). GSH levels were normal in all examined normal and degenerating extra-nigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (antioxidant and product of purine catabolism) also was observed in nigra of all patient groups (-19 to -30%). These data suggest that glutathione depletion, possibly consequent to overutilisation in oxidative stress reactions, could play a causal role in nigral degeneration in all nigrostriatal dopamine deficiency disorders, and that antioxidant therapeutic approaches should not be restricted to PD.