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Mutations in alpha-synuclein, parkin and ubiquitin C-terminal hydrolase L1, and defects in 26/20S proteasomes, cause or are associated with the development of familial and sporadic Parkinson's disease (PD). This suggests that failure of the ubiquitin-proteasome system (UPS) to degrade abnormal proteins may underlie nigral degeneration and Lewy body(More)
Oxidative stress is thought to play an important role in the pathogenesis of Parkinson's disease (PD). Glutathione (GSH), a major cellular antioxidant, is decreased in the substantia nigra pars compacta of PD patients. The aim of the present study was to investigate whether deprenyl and its desmethyl metabolite, putative neuroprotective agents in the(More)
Glutathione (GSH) is a ubiquitous cellular sulfhydryl compound with a variety of essential functions. A histochemical method that was developed by others for the localization of GSH in tissue sections was used to study the localization of GSH in rodent and primate brain. Sections of freshly frozen tissue were stained for 4 min with Mercury orange dissolved(More)
We have examined the role of glial cells in the toxicity that results from inhibition of reduced glutathione (GSH) synthesis by L-buthionine sulfoximine (BSO) in mesencephalic cell cultures. We show that GSH depletion, to levels that cause total cell loss in cultures containing neurons and glial cells, has no effect on cell viability in enriched neuronal(More)
1-Methyl-4-phenylpyridinium ion (MPP+) is the product of the metabolic oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidase (MAO). MPP+ is toxic to 3,4-dihydroxyphenylethylamine (dopamine, DA) neurons in explant cultures of rat embryonic midbrain. Addition of 2.5 microM MPP+ to the feeding medium for 6 days results in(More)
Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease (PD) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this(More)
Release of 3H-doapamine or of 3H-norepinephrine and inhibition of accumulation of 3H-dopamine or 3H-norepinephrine by d- and l-amphetamine were studied in slices of rat neostriatum and in slices of rat cerebral cortex. The two stereoisomers of amphetamine were equally potent as inhibitors of accumulation in the cortex, whereas d-amphetamine was(More)