Proteasome inhibitor-induced model of Parkinson's disease.
We recently reported that systemic administration of a proteasome inhibitor induced a progressive levodopa-responsive, bradykinetic syndrome in rats with imaging, pathological, and biochemical features that strikingly resemble what is found in PD. This model has the potential to be a useful tool for studying the mechanism of cell death in Parkinson's disease and for testing putative neuroprotective agents. Since publication of these findings, several laboratories have sought to reproduce the model; some have been successful in replicating our findings, but others have not. The reason for this variability is not known, but resolution is critically important given the potential utility of this model. We have begun to examine various factors that alone or in combination might explain these differences, and we present in this article preliminary results from these studies.
McNaught
Kevin St P
KS
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA. kevin.mcnaught@mssm.edu
Olanow
C Warren
CW
D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D009842:Oligopeptides / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D025801:Ubiquitin / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects
D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D025801:Ubiquitin; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal