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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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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