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

Journal of Pharmacological Sciences

Takahiro Taira¹  Kazunori Takahashi²  Masatoshi Inden⁴  Rina Niwa⁴  Takashi Taniguchi⁴  Toshio Honda²  Hiroyoshi Ariga³  Risa Funayama⁴  Kazuyuki Takata⁴  Natsuko Ito⁴  Yoshihisa Kitamura⁴  Kaneyasu Nishimura⁴ 

[1] Department of Molecular Cell Biology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan;Faculty of Pharmaceutical Sciences, Hoshi University, Japan;Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan;Department of Neurobiology, Kyoto Pharmaceutical University, Japan

关键词: Parkinson’s disease;    DJ-1;    6-hydroxydopamine;    rotenone;    neuroprotection;   

DOI  :  10.1254/jphs.11151FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(52)Cited-By(9)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.

【 授权许可】

Unknown