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

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

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

DOI：10.3390/ijms10114789

• DJ-1
• allosteric modulator
• neuroprotection
• anti-oxidative response
• in silico virtual screening
• in vivo rat brain
• in vitro neuronal culture

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.