Abstract
Dysfunction of the ubiquitin-proteasomal system (UPS) has been implicated in the pathogenesis of Parkinson's disease. The systemic administration of UPS inhibitors has been reported to induce nigrostriatal cell death and model Parkinson's disease pathology in rodents. We administered a synthetic, specific UPS inhibitor (PSI) subcutaneously to rats and quantified substantia nigral tyrosine hydroxylase-positive dopaminergic neurons by stereology. PSI caused a 15% decrease in UPS activity at 2 weeks and a 42% reduction in substantia nigra pars compacta tyrosine hydroxylase-positive neurons at 8 weeks. Systemic inhibition of the UPS warrants further evaluation as a means to model Parkinson's disease.
Publication types
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Comment
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal / drug effects
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Brain Chemistry / drug effects
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Chymotrypsin / metabolism
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Cysteine Proteinase Inhibitors / pharmacology*
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Grooming / drug effects
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Hand Strength
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Motor Activity / drug effects
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Muscle Tonus / drug effects
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Neurons / enzymology*
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Oligopeptides / pharmacology*
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Postural Balance / drug effects
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Proteasome Endopeptidase Complex / drug effects
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Rats
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Rats, Sprague-Dawley
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Reflex / drug effects
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Substantia Nigra / cytology*
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Substantia Nigra / enzymology*
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Tyrosine 3-Monooxygenase / metabolism*
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Weight Gain / drug effects
Substances
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Cysteine Proteinase Inhibitors
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Oligopeptides
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benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal
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Tyrosine 3-Monooxygenase
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Chymotrypsin
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Proteasome Endopeptidase Complex