Proteasome Inhibitors Protect Against Degeneration of Nigral Dopaminergic Neurons in Hemiparkinsonian Rats
スポンサーリンク
概要
- 論文の詳細を見る
Parkinson’s disease is characterized by dopaminergic neuronal death and the presence of Lewy bodies in the substantia nigra pars compacta (SNpc). α-Synuclein and ubiquitin are components of Lewy bodies, but the process of Lewy body formation and the relationship between inclusion formation and dopaminergic neuronal death have not been resolved. In this study, unilateral intranigral microinjection of 6-hydroxydopamine caused a significant loss of tyrosine hydroxylase-immunopositive neurons in both the substantia nigra and striatum and apomorphine-induced contralateral rotation. The co-administration of proteasome inhibitors, such as lactacystin or carbobenzoxy-<sc>L</sc>-leucyl-<sc>L</sc>-leucyl-<sc>L</sc>-leucinal (MG-132), significantly prevented both dopaminergic neurodegeneration and apomorphine-induced rotational asymmetry. Proteasome inhibitors markedly formed intracellular protein inclusions labeled by thioflavin-S in the SNpc. Inclusion-like immunoreactivities for α-synuclein and ubiquitin were detected after 4 weeks. These results suggest that proteasome plays an important role in both the early phase of dopaminergic neuronal death and inclusion body formation.
- 社団法人 日本薬理学会の論文
- 2005-02-20
著者
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Sawada Hideyuki
京都大学 医学研究科脳病態生理学講座臨床神経学
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Sawada Hideyuki
Department Of Neurology Graduate School Of Medicine Kyoto University
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Takata Kazuyuki
Faculty Of Pharmaceutical Sciences Hoshi University
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Taniguchi Takashi
Department of Geophysics, Faculty of Science, Hokkaido University
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Taniguchi T
Department Of Neurobiology Kyoto Pharmaceutical University
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Takahashi Kazunori
京都薬科大学 病態生理学
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Taniguchi Takashi
京都薬科大学 病態生理学
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Shimohama Shun
Department of Neurology, Sapporo Medical University School of Medicine
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KITAMURA Yoshihisa
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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Shimohama S
Kyoto Univ. Kyoto Jpn
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Shimohama Shun
Department Of Neurology Faculty Of Medicine Kyoto University
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Kondo Jun-ichi
Department Of Neurobiology Kyoto Pharmaceutical University
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INDEN Masatoshi
Department of Neurobiology, Kyoto Pharmaceutical University
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TAKATA Kazuyuki
Department of Neurobiology, Kyoto Pharmaceutical University
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NISHIMURA Kaneyasu
Department of Neurobiology, Kyoto Pharmaceutical University
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Takata Kazuyuki
Department Of Mechanical Engineering Aichi Institute Of Technology
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Inden Masatoshi
Department Of Neurobiology And 21st Century Coe Program Kyoto Pharmaceutical University
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Takeuchi Kosei
Kan Research Institute Inc. Kobe Mi R&d Center
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Takenawa Tadaomi
Division Of Biochemistry Institute Of Medical Science University Of Tokyo
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Kakimura Jun-ichi
Department Of Neurophysiology Graduate School Of Biomedical Sciences Hiroshima University
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Kanai Yoshihito
Department Of Pharmaceutical Care And Health Sciences Okayama University Graduate School Of Medicine
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Kitamura Yoshihisa
Department Of Neurobiology Kyoto Pharmaceutical University
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Kitamura Yoshihisa
Department Of Pharmacology Research Institute For Wakan-yaku Toyama Medical And Pharmaceutical Unive
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Kitamura Y
Department Of Neurobiology Kyoto Pharmaceutical University
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Kitamura Y
Shimizu Pharmaceutical Co. Ltd. Shizuoka Jpn
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Taira Takahiro
Graduate School Of Pharmaceutical Sciences Hokkaido University:crest Japan Science And Technology Co
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Sanada Hisakazu
Department Of Neurology Graduate School Of Medicine Kyoto University
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Sawada Hideyuki
Department Of Anesthesiology Kanagawa Dental College
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Takano T
Dep. Of Neurobiology Kyoto Pharmaceutical Univ.
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Taniguchi Takashi
Department Of Geophysics Faculty Of Science Hokkaido University
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Nakamura K
Department Of Neurobiology Kyoto Pharmaceutical University
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Taniguchi Takashi
Department Of Dermatology Faculty Of Medicine University Of Tokyo
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Inden Masatoshi
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University
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Takata Kazuyuki
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University
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TANIGUCHI Takashi
Department of Computational Science and Engineering, Nagoya University
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Kitamura Yoshihisa
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Japan
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Nishimura Kaneyasu
Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University
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Taniguchi Takashi
Department of Biology, Kyoto Pharmaceutical University
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KITAMURA Yoshihisa
Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
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