Portal de Periódicos da CAPES

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

2009; Multidisciplinary Digital Publishing Institute; Volume: 10; Issue: 11 Linguagem: Inglês

10.3390/ijms10114789

1661-6596

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

Ginkgo biloba and Cashew Applications

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.