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
Journal of Pharmacological Sciences 2009, 109 (3): 463-8
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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