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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

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Title: 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
Authors: Yamane, Koichiro Browse this author
Kitamura, Yoshihisa Browse this author
Yanagida, Takashi Browse this author
Takata, Kazuyuki Browse this author
Yanagisawa, Daijiro Browse this author
Taniguchi, Takashi Browse this author
Taira, Takahiro Browse this author
Ariga, Hiroyoshi Browse this author →KAKEN DB
Keywords: DJ-1
allosteric modulator
neuroprotection
anti-oxidative response
in silico virtual screening
in vivo rat brain
in vitro neuronal culture
Issue Date: Nov-2009
Publisher: MDPI Publishing
Journal Title: International Journal of Molecular Sciences
Volume: 10
Issue: 11
Start Page: 4789
End Page: 4804
Publisher DOI: 10.3390/ijms10114789
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.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/40077
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 有賀 寛芳

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