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

Jeffrey H. Kordower, Nicholas M. Kanaan, Yaping Chu, Rangasamy Suresh Babu, James Stansell, Brian T. Terpstra, Caryl E. Sortwell, Kathy Steece-Collier, Timothy J. Collier

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

McNaught and colleagues' reported recently that systemic administration of proteasome inhibitors PSI (Z-Ileu-Glu(OiBu)-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.

Original languageEnglish (US)
Pages (from-to)264-268
Number of pages5
JournalAnnals of Neurology
Volume60
Issue number2
DOIs
StatePublished - Aug 2006
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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