Protection against oxidative stress-induced neurodegeneration by a modulator for DJ-1, the wild-type of familial Parkinson's disease-linked PARK7.
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.
Yanagida
Takashi
T
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Kitamura
Yoshihisa
Y
Yamane
Koichiro
K
Takahashi
Kazunori
K
Takata
Kazuyuki
K
Yanagisawa
Daijiro
D
Yasui
Hiroyuki
H
Taniguchi
Takashi
T
Taira
Takahiro
T
Honda
Toshio
T
Ariga
Hiroyoshi
H
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D052117:Benzodioxoles / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D006861:Hydrogen Peroxide; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000517:prevention & control; D009447:Neuroblastoma / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015513:Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D001549:Benzamides; D052117:Benzodioxoles; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; C540764:UCP0054278; D006861:Hydrogen Peroxide; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1