title: 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.
abstract: 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.
authors: Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors: Masatoshi
authors: M
authors: Inden
authors: Yoshihisa
authors: Y
authors: Kitamura
authors: Kazunori
authors: K
authors: Takahashi
authors: Kazuyuki
authors: K
authors: Takata
authors: Natsuko
authors: N
authors: Ito
authors: Rina
authors: R
authors: Niwa
authors: Risa
authors: R
authors: Funayama
authors: Kaneyasu
authors: K
authors: Nishimura
authors: Takashi
authors: T
authors: Taniguchi
authors: Toshio
authors: T
authors: Honda
authors: Takahiro
authors: T
authors: Taira
authors: Hiroyoshi
authors: H
authors: Ariga
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D052117:Benzodioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D039481:CD11b Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009498:Neurotoxins; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D001549:Benzamides; D052117:Benzodioxoles; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D015513:Oncogene Proteins; C540764:UCP0054278; D012402:Rotenone; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1