Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 109, Issue 3, Pages 463-468Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.08323SC
Keywords
DJ-1 modulator; anti-oxidative effect; neuroprotection
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
- National Institute of Biomedical Innovation (NIBIO) in Japan
- Grants-in-Aid for Scientific Research [21390014] Funding Source: KAKEN
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Although a loss-of-function type mutation was 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 found a DJ-1 modulator UCP0054278 by in silico virtual screening. In this study, we determined the neuroprotective effects of UCP0054278 against focal ischemia-induced neurodegeneration in rats. Hydrogen peroxide-induced cell death and the production of reactive oxygen species were significantly inhibited by UCP0054278 in normal SH-SY5Y cells, but not in DJ-1-knockdown cells. These results suggest that UCP0054278 interacts with endogenous DJ-1 and then exhibits antioxidant and neuroprotective responses.
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