Proteasome inhibition and Parkinson's disease modeling.
Impaired proteasome function is a potential mechanism for dopaminergic neuron degeneration. To model this molecular defect, we administered systemically the reversible lipophilic proteasome inhibitor, carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI), to rodents. In contrast to a previous report, this approach failed to cause any detectable behavioral or neuropathological abnormality in either rats or mice. Although theoretically appealing, this specific model of Parkinson's disease appears to exhibit poor reproducibility.
Bové
Jordi
J
Department of Neurology, Columbia University, New York, NY, USA.
Zhou
Chun
C
Jackson-Lewis
Vernice
V
Taylor
Julie
J
Chu
Yaping
Y
Rideout
Hardy J
HJ
Wu
Du-Chu
DC
Kordower
Jeffrey H
JH
Petrucelli
Leonard
L
Przedborski
Serge
S
D000818:Animals; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; D049452:Green Fluorescent Proteins; D014446:Tyrosine 3-Monooxygenase