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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)
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)
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)
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)
L-Deprenyl is a relatively selective inhibitor of monoamine oxidase (MAO)-B that delays the emergence of disability and the progression of signs and symptoms of Parkinson's disease. Experimentally, deprenyl has also been shown to prevent neuronal cell death in various models through a mechanism that is independent of MAO-B inhibition. We examined the effect(More)
Recent studies showed that the Alzheimer amyloid precursor (APP) occurs as the core protein of a chondroitin sulfate proteoglycan (appican) in C6 glioma cells. In the present study we show that appican is present in both human and rat brain tissue. Cortical rat brain cell cultures were used to identify appican-producing cells. Soluble secreted and(More)
Epidermal growth factor (EGF) immunoreactive material has been demonstrated to be present in the basal ganglia. In this study, we investigated the effect of EGF on cells cultured from 16-day embryonic rat mesencephalon, which included dopamine neurons that project to the striatum in vivo. EGF receptors were detected in untreated cultures by [125I]-EGF(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)