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

Yamane, Koichiro; Kitamura, Yoshihisa; Yanagida, Takashi; Takata, Kazuyuki; Yanagisawa, Daijiro; Taniguchi, Takashi; Taira, Takahiro; Ariga, Hiroyoshi

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

Yamane, Koichiro; Kitamura, Yoshihisa; Yanagida, Takashi et al.

International Journal of Molecular Sciences, 2009, 10(11), 4789-4804

Permalink : https://hdl.handle.net/2115/40077

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アクセス権	open access
URI	https://hdl.handle.net/2115/40077
タイトル	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
著者	Yamane, Koichiro ; Kitamura, Yoshihisa ; Yanagida, Takashi ; Takata, Kazuyuki ; Yanagisawa, Daijiro ; Taniguchi, Takashi ; Taira, Takahiro ; Ariga, Hiroyoshi
著者名 Yamane, Koichiro
著者名 Kitamura, Yoshihisa
著者名 Yanagida, Takashi
著者名 Takata, Kazuyuki
著者名 Yanagisawa, Daijiro
著者名 Taniguchi, Takashi
著者名 Taira, Takahiro
e-Rad_Researcher 20143505 著者名 Ariga, Hiroyoshi
言語	英語
キーワード	DJ-1
	allosteric modulator
	neuroprotection
	anti-oxidative response
	in silico virtual screening
	in vivo rat brain
	in vitro neuronal culture
発行日	2009-11
出版者	MDPI Publishing
収録物名	International Journal of Molecular Sciences
巻(号)	10(11)
ページ	4789-4804
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1422-0067
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3390/ijms10114789