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

International Journal of Molecular Sciences

Koichiro Yamane²  Yoshihisa Kitamura²  Takashi Yanagida²  Kazuyuki Takata²  Daijiro Yanagisawa²  Takashi Taniguchi²  Takahiro Taira¹ 

[1] Department of Molecular Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, Japan; E-Mail:;Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan; E-Mails:

关键词: DJ-1;    allosteric modulator;    neuroprotection;    anti-oxidative response;    in silico virtual screening;    in vivo rat brain;    in vitro neuronal culture;   

DOI  :  10.3390/ijms10114789

来源: mdpi

【 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.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.