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

被引：15

作者：

Yamane, Koichiro ^{[1
]}

Kitamura, Yoshihisa ^{[1
]}

Yanagida, Takashi ^{[1
]}

Takata, Kazuyuki ^{[1
]}

Yanagisawa, Daijiro ^{[1
]}

Taniguchi, Takashi ^{[1
]}

Taira, Takahiro ^{[2
]}

Ariga, Hiroyoshi ^{[3
]}

机构：

[1] Kyoto Pharmaceut Univ, Dept Neurobiol, Kyoto 6078414, Japan

[2] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Dept Mol Cell Biol, Chuo 4093898, Japan

[3] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Mol Biol, Sapporo, Hokkaido 060812, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2009年 / 10卷 / 11期

关键词：

DJ-1; allosteric modulator; neuroprotection; anti-oxidative response; in silico virtual screening; in vivo rat brain; in vitro neuronal culture; CEREBRAL-ARTERY OCCLUSION; CRYSTAL-STRUCTURE; CELL-DEATH; ALPHA-SYNUCLEIN; ANTIOXIDATIVE STRESS; ANDROGEN RECEPTOR; PROTEIN; RAT; ISCHEMIA; BRAIN;

D O I：

10.3390/ijms10114789

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4789 / 4804

页数：16

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