2024-03-29T04:46:41Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/400772022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124Oxidative Neurodegeneration Is Prevented by UCP0045037, an Allosteric Modulator for the Reduced Form of DJ-1, a Wild-Type of Familial Parkinson's Disease-Linked PARK7Yamane, KoichiroKitamura, YoshihisaYanagida, TakashiTakata, KazuyukiYanagisawa, DaijiroTaniguchi, TakashiTaira, TakahiroAriga, HiroyoshiDJ-1allosteric modulatorneuroprotectionanti-oxidative responsein silico virtual screeningin vivo rat brainin vitro neuronal culture499Although 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.MDPI PublishingJournal Articleapplication/pdfhttp://hdl.handle.net/2115/40077https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/40077/1/IJMS10-11_4789-4804.pdf1422-0067International Journal of Molecular Sciences1011478948042009-11enginfo:doi/10.3390/ijms10114789http://creativecommons.org/licenses/by/3.0/publisher