Proteasome inhibition in medaka brain induces the features of Parkinson's disease

Journal of Neurochemistry
Hideaki MatsuiRyosuke Takahashi

Abstract

Recent findings suggest that a defect in the ubiquitin-proteasome system plays an important role in the pathogenesis of Parkinson's disease (PD). A previous report (McNaught et al. 2004) demonstrated that rats systemically injected with proteasome inhibitors exhibited PD-like clinical symptoms and pathology. However, because these findings have not been consistently replicated, this model is not commonly used to study PD. We used medaka fish to test the effect of systemic administration of proteasome inhibitors because of the high level of accessibility of the cerebrospinal fluid in fish. We injected lactacystin or epoxomicin into the CSF of medaka. With proteasome inhibition in the medaka brain, selective dopaminergic and noradrenergic cell loss was observed. Furthermore, treated fish exhibited reduced spontaneous movement. Treatment with proteasome inhibitors also induced the formation of inclusion bodies resembling Lewy bodies, which are characteristic of PD. Treatment with 6-OHDA also induced dopaminergic cell loss but did not produce inclusion bodies. These findings in medaka are consistent with previous results reporting that non-selective proteasome inhibition replicates the cardinal features of PD: locomotor dysfunction...Continue Reading

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Citations

Jun 30, 2012·Acta Neuropathologica·Darius Ebrahimi-FakhariPamela J McLean
Oct 26, 2012·The Journal of Biological Chemistry·Yoshitaka TashiroRyosuke Takahashi
Mar 2, 2013·Human Molecular Genetics·Hideaki MatsuiRyosuke Takahashi
Feb 2, 2016·Free Radical Biology & Medicine·Zsolt RadakErika Koltai
Jul 23, 2013·Free Radical Research·Z RadakI Boldogh
Nov 2, 2016·Journal of Parkinson's Disease·Eduard BenteaAnn Massie
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May 27, 2017·Development, Growth & Differentiation·Hideaki Matsui
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Sep 3, 2017·Journal of Neural Transmission·Hideaki Matsui, Noriko Matsui
Oct 12, 2012·Experimental Neurobiology·Hideaki MatsuiRyosuke Takahashi
Aug 5, 2017·Journal of Neural Transmission·Hideaki Matsui, Ryosuke Takahashi
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Nov 20, 2016·Bioscience, Biotechnology, and Biochemistry·Yuki TakadaKiyotaka Hitomi
Sep 8, 2017·PloS One·Hideaki Matsui, Atsushi Sugie
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Feb 12, 2021·Zebrafish·Louise Oliveira FiamettiLeandro Mantovani de Castro

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