PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model.
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.
Inden
Masatoshi
M
Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Taira
Takahiro
T
Kitamura
Yoshihisa
Y
Yanagida
Takashi
T
Tsuchiya
Daiju
D
Takata
Kazuyuki
K
Yanagisawa
Daijiro
D
Nishimura
Kaneyasu
K
Taniguchi
Takashi
T
Kiso
Yoshiaki
Y
Yoshimoto
Kanji
K
Agatsuma
Tomohiro
T
Koide-Yoshida
Shizuyo
S
Iguchi-Ariga
Sanae M M
SM
Shimohama
Shun
S
Ariga
Hiroyoshi
H
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D017072:Neostriatum / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents; D015513:Oncogene Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D016627:Oxidopamine; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D013378:Substantia Nigra / Q000502:physiology*; D013565:Sympatholytics
D019138:Antibodies, Blocking; D015259:Dopamine Agents; D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013565:Sympatholytics; D016627:Oxidopamine; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D005978:Glutathione; D004298:Dopamine