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Failure of proteasome inhibitor administration to provide a model of Parkinson's disease in rats and monkeys
Author(s) -
Kordower Jeffrey H.,
Kanaan Nicholas M.,
Chu Yaping,
Suresh Babu Rangasamy,
Stansell James,
Terpstra Brian T.,
Sortwell Caryl E.,
SteeceCollier Kathy,
Collier Timothy J.
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20935
Subject(s) - nucleus basalis , substantia nigra , proteasome inhibitor , dopamine , locus ceruleus , locus coeruleus , proteasome , parkinson's disease , pharmacology , neuroscience , caudate nucleus , biology , disease , medicine , endocrinology , nucleus , central nervous system , microbiology and biotechnology , cholinergic neuron
McNaught and colleagues1 reported recently that systemic administration of proteasome inhibitors PSI (Z‐Ileu‐Glu(O t Bu)‐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