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

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

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  • Protection against oxidative stress-induced neurodegeneration by a modulator for DJ-1, a wild-type of familial Parkinson’s disease-linked PARK7

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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.<br>

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