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Proteasomal inhibition causes loss of nigral tyrosine hydroxylase neurons
Author(s) -
Schapira Anthony H. V.,
Cleeter Michael W. J.,
Muddle John R.,
Workman Jane M.,
Cooper J. Mark,
King Rosalind H. M.
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20934
Subject(s) - substantia nigra , pars compacta , tyrosine hydroxylase , parkinson's disease , dopaminergic , pathogenesis , tyrosine 3 monooxygenase , endocrinology , neuroscience , medicine , tyrosine , dopamine , chemistry , biology , disease , biochemistry
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. Ann Neurol 2006;60:253–255