PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson’s disease rat model

Neurobiology of Disease

Yoshihisa Kitamura¹  Shun Shimohama²  Hiroyoshi Ariga³  Tomohiro Agatsuma⁴  Kanji Yoshimoto⁵  Sanae M.M. Iguchi-Ariga⁶  Takahiro Taira⁶  Shizuyo Koide-Yoshida⁶  Daijiro Yanagisawa⁷  Daiju Tsuchiya⁷  Kaneyasu Nishimura⁷  Yoshiaki Kiso⁷  Takashi Yanagida⁷  Masatoshi Inden⁷  Takashi Taniguchi⁷  Kazuyuki Takata⁷ 

[1] CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan;Department of Medical Chemistry, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan;CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan;Department of Legal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;Department of Medical Chemistry, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan;Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan;Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan;

关键词: DJ-1;    Parkinson’s disease;    Oxidative stress;    Cell death;    Reactive oxygen species;   

DOI  :  

来源: DOAJ

【 摘 要 】

DJ-1 has recently been shown to be responsible for onset of familial Parkinson’s disease (PD), PARK7. DJ-1 has been shown to play roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD. In this study, a recombinant DJ-1 protein was administrated into the brain of PD model rats that had been injected to 6-hydroxydopamine (6-OHDA) in the left substantia nigra. PD phenotypes, including dopaminergic neuron death in the substantia nigra, decrease in dopamine, and dopamine transporter levels in the striatum, and motor abnormality, were dramatically improved by wild-type DJ-1 but not L166P DJ-1, a mutant form of DJ-1 found in PD patients. Furthermore, production of reactive oxygen species and cell death induced by 6-OHDA in SH-SY5Y cells and mesencephalic neurons were inhibited by addition of the recombinant DJ-1. These findings suggest that DJ-1 is a therapeutic target for PD.

【 授权许可】

Unknown