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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
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| Title: | 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 |
| Authors: | Yamane, Koichiro Browse this author | | Kitamura, Yoshihisa Browse this author | | Yanagida, Takashi Browse this author | | Takata, Kazuyuki Browse this author | | Yanagisawa, Daijiro Browse this author | | Taniguchi, Takashi Browse this author | | Taira, Takahiro Browse this author | | Ariga, Hiroyoshi Browse this author →KAKEN DB |
| Keywords: | DJ-1 | | allosteric modulator | | neuroprotection | | anti-oxidative response | | in silico virtual screening | | in vivo rat brain | | in vitro neuronal culture |
| Issue Date: | Nov-2009 |
| Publisher: | MDPI Publishing |
| Journal Title: | International Journal of Molecular Sciences |
| Volume: | 10 |
| Issue: | 11 |
| Start Page: | 4789 |
| End Page: | 4804 |
| Publisher DOI: | 10.3390/ijms10114789 |
| Abstract: | 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. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/40077 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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