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

Masatoshi Inden; Takahiro Taira; Yoshihisa Kitamura; Takashi Yanagida; Daiju Tsuchiya; Kazuyuki Takata; Daijiro Yanagisawa; Kaneyasu Nishimura; Takashi Taniguchi; Yoshiaki Kiso; Kanji Yoshimoto; Tomohiro Agatsuma; Shizuyo Koide-Yoshida; Sanae M.M. Iguchi-Ariga; Shun Shimohama; Hiroyoshi Ariga

Neurobiology of Disease (Oct 2006)

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

Masatoshi Inden,
Takahiro Taira,
Yoshihisa Kitamura,
Takashi Yanagida,
Daiju Tsuchiya,
Kazuyuki Takata,
Daijiro Yanagisawa,
Kaneyasu Nishimura,
Takashi Taniguchi,
Yoshiaki Kiso,
Kanji Yoshimoto,
Tomohiro Agatsuma,
Shizuyo Koide-Yoshida,
Sanae M.M. Iguchi-Ariga,
Shun Shimohama,
Hiroyoshi Ariga

Affiliations

Masatoshi Inden: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Takahiro Taira: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan
Yoshihisa Kitamura: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Takashi Yanagida: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Daiju Tsuchiya: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Kazuyuki Takata: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Daijiro Yanagisawa: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Kaneyasu Nishimura: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Takashi Taniguchi: Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan
Yoshiaki Kiso: Department of Medical Chemistry, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan
Kanji Yoshimoto: Department of Legal Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
Tomohiro Agatsuma: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Shizuyo Koide-Yoshida: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; Department of Medical Chemistry, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan
Sanae M.M. Iguchi-Ariga: CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan; Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan
Shun Shimohama: Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
Hiroyoshi Ariga: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; CREST, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan; Corresponding author. Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Fax: +81 11 706 4988.

Journal volume & issue: Vol. 24, no. 1
pp. 144 – 158

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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