Lack of nigrostriatal pathology in a rat model of proteasome inhibition - PubMed (original) (raw)

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Lack of nigrostriatal pathology in a rat model of proteasome inhibition

Amy B Manning-Boğ et al. Ann Neurol. 2006 Aug.

Abstract

Systemic administration of ubiquitin-proteasome system inhibitors to rodents has been reported to induce certain behavioral and neuropathological features of Parkinson's disease. The goal of this study was to replicate these observations by administering a proteasome inhibitor (PSI) to rats using McNaught and colleagues' protocol. No alterations in locomotor activity or striatal dopamine and its metabolites were observed. Differences in nigral dopaminergic cell number between proteasome inhibitor- and vehicle-treated rats and inclusion bodies were not found. Extending the time of survival after administration and using different solvents failed to alter results, indicating this proteasome inhibitor does not consistently produce the selective toxicity and pathological hallmarks characterizing 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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