Oxidative Neurodegeneration Is Prevented by UCP0045037, an Allosteric Modulator for the Reduced Form of DJ-1, a Wild-Type of Familial Parkinson's Disease-Linked PARK7
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概要
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Although a loss-of-function mutation has been 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 identified UCP0045037 as a compound that bound to the reduced form of DJ-1 by in silico virtual screening. In this study, we determined the neuroprotective effects of UCP0045037 against focal cerebral ischemia-induced neurodegeneration in rats. Hydrogen peroxide-induced cell death was significantly inhibited by UCP0045037 in both rat mesencephalic dopaminergic neurons and human normal SH-SY5Y cells. In contrast, DJ-1-knockdown SH-SY5Y cells lost the protective activity of UCP0045037. These results suggest that UCP0045037 interacts with endogenous DJ-1 and produces a neuroprotective response.
著者
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Takata Kazuyuki
Faculty Of Pharmaceutical Sciences Hoshi University
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Taniguchi T
Department Of Neurobiology Kyoto Pharmaceutical University
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Takahashi Kazunori
京都薬科大学 病態生理学
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Taniguchi Takashi
京都薬科大学 病態生理学
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Yanagisawa Daijiro
Department Of Neurobiology Kyoto Pharmaceutical University
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YANAGIDA Takashi
Department of Neurobiology, Kyoto Pharmaceutical University
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YAMANE Koichiro
Department of Neurobiology, Kyoto Pharmaceutical University
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Takeuchi Kosei
Kan Research Institute Inc. Kobe Mi R&d Center
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Yamane Koichiro
Department Of Neurobiology Kyoto Pharmaceutical University
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Takenawa Tadaomi
Division Of Biochemistry Institute Of Medical Science University Of Tokyo
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Yanagida Takashi
Department Of Neurobiology Kyoto Pharmaceutical University
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Kanai Yoshihito
Department Of Pharmaceutical Care And Health Sciences Okayama University Graduate School Of Medicine
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Kitamura Yoshihisa
Department Of Neurobiology Kyoto Pharmaceutical University
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Kitamura Yoshihisa
Department Of Pharmacology Research Institute For Wakan-yaku Toyama Medical And Pharmaceutical Unive
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Kitamura Y
Department Of Neurobiology Kyoto Pharmaceutical University
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Kitamura Y
Shimizu Pharmaceutical Co. Ltd. Shizuoka Jpn
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Taira Takahiro
Graduate School Of Pharmaceutical Sciences Hokkaido University:crest Japan Science And Technology Co
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Ariga Hiroyoshi
Laboratory Of Molecular Biolgy Graduate School Of Pharmaceutical Sciences Hokkaido University
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Ariga Hiroyoshi
Graduate School Of Pharmaceutical Sciences Hokkaido University
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Ariga Hiroyoshi
Graduate School Of Pharmaceutical Sciences Hokkaido University:crest Japan Science And Technology Co
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Takano T
Dep. Of Neurobiology Kyoto Pharmaceutical Univ.
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Ariga H
Graduate School Of Pharmaceutical Sciences Hokkaido University
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