Failure of proteasome inhibitor administration to provide a model of Parkinson's disease in rats and monkeys - PubMed (original) (raw)

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

Jeffrey H Kordower et al. Ann Neurol. 2006 Aug.

Abstract

McNaught and colleagues 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.

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• Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease.
  McNaught KS, Perl DP, Brownell AL, Olanow CW. McNaught KS, et al. Ann Neurol. 2004 Jul;56(1):149-62. doi: 10.1002/ana.20186. Ann Neurol. 2004. PMID: 15236415

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