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Failure of proteasome inhibitor administration to provide a model of Parkinson's disease in rats and monkeys

McNaught and colleagues1 reported recently that systemic administration of proteasome inhibitors PSI (Z‐Ileu‐Glu(OtBu)‐Ala‐Leu‐CHO) or epoxomicin recapitulated many of the degenerative changes seen in Parkinson's disease including loss of striatal dopamine and cell loss in the substantia nigra,...

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Bibliographic Details
Published in:Annals of neurology 2006-08, Vol.60 (2), p.264-268
Main Authors: Kordower, Jeffrey H., Kanaan, Nicholas M., Chu, Yaping, Suresh Babu, Rangasamy, Stansell III, James, Terpstra, Brian T., Sortwell, Caryl E., Steece-Collier, Kathy, Collier, Timothy J.
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Language:English
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Summary:McNaught and colleagues1 reported recently that systemic administration of proteasome inhibitors PSI (Z‐Ileu‐Glu(OtBu)‐Ala‐Leu‐CHO) or epoxomicin recapitulated many of the degenerative changes seen in Parkinson's disease including loss of striatal dopamine and cell loss in the substantia nigra, locus ceruleus, dorsal motor nucleus of the X cranial nerve, and nucleus basalis of Meynert. Intracytoplasmic inclusions resembling Lewy bodies were also described. All experiments administering PSI to rats using identical procedures and multiple attempts failed to induce any of the previously described changes. Furthermore, administration of PSI or epoxomicin to monkeys in an attempt to extend the model to a primate species failed. Currently, systemic proteasome inhibition is not a reliable model for Parkinson's disease. Ann Neurol 2006;60:264–268
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.20935