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

2009; Elsevier BV; Volume: 109; Issue: 3 Linguagem: Inglês

10.1254/jphs.08323sc

1347-8648

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

Medicinal Plants and Neuroprotection

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.