RGD Reference Report - Protection against dopaminergic neurodegeneration in Parkinson's disease-model animals by a modulator of the oxidized form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7.

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Protection against dopaminergic neurodegeneration in Parkinson's disease-model animals by a modulator of the oxidized form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7.
Authors:	Inden, Masatoshi Kitamura, Yoshihisa Takahashi, Kazunori Takata, Kazuyuki Ito, Natsuko Niwa, Rina Funayama, Risa Nishimura, Kaneyasu Taniguchi, Takashi Honda, Toshio Taira, Takahiro Ariga, Hiroyoshi
Citation:	Inden M, etal., J Pharmacol Sci. 2011;117(3):189-203. Epub 2011 Oct 29.
RGD ID:	13462067
Pubmed:	PMID:22041943 (View Abstract at PubMed)
DJ-1, Parkinson's disease PARK7, acts as an oxidative stress sensor in neural cells. Recently, we identified the DJ-1 modulator UCP0054278 by in silico virtual screening. However, the effect of the peripheral administration of UCP0054278 on an in vivo Parkinson's disease (PD) model is unclear. Therefore, in the present study, we examined the effects of the peripheral administration of UCP0054278 on both 6-OHDA-microinjected rats and rotenone-treated mice as acute and chronic animal models of PD, respectively. The peripheral administration of UCP0054278 prevented 6-OHDA- and rotenone-induced dopaminergic neural cell death and restored the defect in locomotion in these models of PD. In addition, 6-OHDA- or rotenone-induced neural 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 produces antioxidant and neuroprotective responses in both in vivo and in vitro models of PD. The present study raises the possibility that DJ-1 stimulatory modulators, such as UCP0054278, may be a new type of dopaminergic neuroprotective drug for the treatment of PD.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PARK7	Human	Parkinsonism	treatment	ISO	Park7 (Rattus norvegicus)		RGD
Park7	Rat	Parkinsonism	treatment	IDA			RGD
Park7	Mouse	Parkinsonism	treatment	ISO	Park7 (Rattus norvegicus)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Park7 (Parkinsonism associated deglycase)

Genes (Mus musculus)

Park7 (Parkinson disease (autosomal recessive, early onset) 7)

Genes (Homo sapiens)

PARK7 (Parkinsonism associated deglycase)

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Protection against dopaminergic neurodegeneration in Parkinson's disease-model animals by a modulator of the oxidized form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7.