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Int. J. Mol. Sci. 2009, 10(11), 4789-4804; doi:10.3390/ijms10114789
Article

Oxidative Neurodegeneration Is Prevented by UCP0045037, an Allosteric Modulator for the Reduced Form of DJ-1, a Wild-Type of Familial Parkinson’s Disease-Linked PARK7

1
,
1,* , 1, 1
,
1, 1
,
2
 and
3,*
1 Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan 2 Department of Molecular Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan 3 Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
* Authors to whom correspondence should be addressed.
Received: 17 September 2009 / Revised: 21 October 2009 / Accepted: 2 November 2009 / Published: 5 November 2009
(This article belongs to the Special Issue Neuroprotective Strategies (special issue))
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Abstract

Although a loss-of-function mutation has been identified in familial Parkinson’s disease PARK7, the wild-type of DJ-1 is known to act as an oxidative stress sensor in neuronal cells. Recently, we identified UCP0045037 as a compound that bound to the reduced form of DJ-1 by in silico virtual screening. In this study, we determined the neuroprotective effects of UCP0045037 against focal cerebral ischemia-induced neurodegeneration in rats. Hydrogen peroxide-induced cell death was significantly inhibited by UCP0045037 in both rat mesencephalic dopaminergic neurons and human normal SH-SY5Y cells. In contrast, DJ-1-knockdown SH-SY5Y cells lost the protective activity of UCP0045037. These results suggest that UCP0045037 interacts with endogenous DJ-1 and produces a neuroprotective response.
Keywords: DJ-1; allosteric modulator; neuroprotection; anti-oxidative response; in silico virtual screening; in vivo rat brain; in vitro neuronal culture DJ-1; allosteric modulator; neuroprotection; anti-oxidative response; in silico virtual screening; in vivo rat brain; in vitro neuronal culture
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Yamane, K.; Kitamura, Y.; Yanagida, T.; Takata, K.; Yanagisawa, D.; Taniguchi, T.; Taira, T.; Ariga, H. Oxidative Neurodegeneration Is Prevented by UCP0045037, an Allosteric Modulator for the Reduced Form of DJ-1, a Wild-Type of Familial Parkinson’s Disease-Linked PARK7. Int. J. Mol. Sci. 2009, 10, 4789-4804.

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