Protection Against Oxidative Stress-Induced Neurodegeneration by a Modulator for DJ-1, the Wild-Type of Familial Parkinson’s Disease-Linked PARK7

Takashi Yanagida; Yoshihisa Kitamura; Koichiro Yamane; Kazunori Takahashi; Kazuyuki Takata; Daijiro Yanagisawa; Hiroyuki Yasui; Takashi Taniguchi; Takahiro Taira; Toshio Honda; Hiroyoshi Ariga

doi:10.1254/jphs.08323SC

Short Communications

Protection Against Oxidative Stress-Induced Neurodegeneration by a Modulator for DJ-1, the Wild-Type of Familial Parkinson’s Disease-Linked PARK7

Takashi Yanagida, Yoshihisa Kitamura, Koichiro Yamane, Kazunori Takahashi, Kazuyuki Takata, Daijiro Yanagisawa, Hiroyuki Yasui, Takashi Taniguchi, Takahiro Taira, Toshio Honda, Hiroyoshi Ariga

Author information

Takashi Yanagida
Department of Neurobiology, Kyoto Pharmaceutical University, Japan
Yoshihisa Kitamura
Department of Neurobiology, Kyoto Pharmaceutical University, Japan
Koichiro Yamane
Department of Neurobiology, Kyoto Pharmaceutical University, Japan
Kazunori Takahashi
Faculty of Pharmaceutical Sciences, Hoshi University, Japan
Kazuyuki Takata
Department of Neurobiology, Kyoto Pharmaceutical University, Japan
Daijiro Yanagisawa
Department of Neurobiology, Kyoto Pharmaceutical University, Japan
Hiroyuki Yasui
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan
Takashi Taniguchi
Department of Neurobiology, Kyoto Pharmaceutical University, Japan
Takahiro Taira
Department of Molecular Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan
Toshio Honda
Faculty of Pharmaceutical Sciences, Hoshi University, Japan
Hiroyoshi Ariga
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan

Keywords: DJ-1 modulator, anti-oxidative effect, neuroprotection

JOURNAL FREE ACCESS

2009 Volume 109 Issue 3 Pages 463-468

DOI https://doi.org/10.1254/jphs.08323SC

View "Advance Publication" version (March 11, 2009).

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Abstract

Although a loss-of-function type mutation was 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 found a DJ-1 modulator UCP0054278 by in silico virtual screening. In this study, we determined the neuroprotective effects of UCP0054278 against focal ischemia-induced neurodegeneration in rats. Hydrogen peroxide–induced cell death and the production of reactive oxygen species were significantly inhibited by UCP0054278 in normal SH-SY5Y cells, but not in DJ-1–knockdown cells. These results suggest that UCP0054278 interacts with endogenous DJ-1 and then exhibits antioxidant and neuroprotective responses.

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