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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
Creator

Yamane, Koichiro

Kitamura, Yoshihisa

Yanagida, Takashi

Takata, Kazuyuki

Yanagisawa, Daijiro

Taniguchi, Takashi

Taira, Takahiro

Ariga, Hiroyoshi

Rights
    • http://creativecommons.org/licenses/by/3.0/
Subject
  • Other DJ-1
  • Other allosteric modulator
  • Other neuroprotection
  • Other anti-oxidative response
  • Other in silico virtual screening
  • Other in vivo rat brain
  • Other in vitro neuronal culture
  • NDC 499
Description
Other
  • 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.
PublisherMDPI Publishing
Date Issued 2009-11
Languageeng
NIItypejournal article
VersiontypeVoR
Identifier URI http://hdl.handle.net/2115/40077
Relation
  • isIdenticalTo DOI https://doi.org/10.3390/ijms10114789
Journal
    • ISSN 1422-0067
    • International Journal of Molecular Sciences
    10(11), 4789-4804
File
Oaidate2012-02-06T10:50:00Z