Proteasome Inhibitors Protect Against Degeneration of Nigral Dopaminergic Neurons in Hemiparkinsonian Rats
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- Inden Masatoshi
- Department of Neurobiology, Kyoto Pharmaceutical University
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- Kondo Jun-ichi
- Department of Neurobiology, Kyoto Pharmaceutical University
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- Kitamura Yoshihisa
- Department of Neurobiology, Kyoto Pharmaceutical University 21st Century COE Program, 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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- Taniguchi Takashi
- Department of Neurobiology, Kyoto Pharmaceutical University 21st Century COE Program, Kyoto Pharmaceutical University
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- Sawada Hideyuki
- Department of Neurology, Graduate School of Medicine, Kyoto University
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- Shimohama Shun
- Department of Neurology, Graduate School of Medicine, Kyoto University
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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.<br>
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 97 (2), 203-211, 2005
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205175634816
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- NII論文ID
- 10025725946
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 7258377
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- PubMed
- 15684568
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可