The analysis of participation in the ubiquitin proteasome system for understanding the mechanisms of neurodegenerative diseases.
Project/Area Number |
20390244
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Kyoto University |
Principal Investigator |
TAKAHASHI Ryosuke Kyoto University, 医学研究科, 教授 (90216771)
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Co-Investigator(Kenkyū-buntansha) |
INOUE Haruhisa 京都大学, 医学研究科, 助教 (70332327)
KAWAMATA Jun 札幌医科大学, 医学部, 講師 (60360814)
MISAWA Hidemi 慶応義塾大学, 薬学部, 教授 (80219617)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
|
Keywords | ALS / 運動ニューロン / プロテアソーム / Rpt3 / コンディショナルノックアウト / 神経変性疾患 / モデル動物 / パーキンソン病 / 筋萎縮性側索硬化症 / RP t 3 / 26Sプロテアソーム / コンディショナルノックアウトマウス / VAChT-Cre / アルツハイマー病 / タンパク分解 / Cre-lox system |
Research Abstract |
We have established motor neuron-specific proteasome deficient mice by crossbreeding of flexed mice for Rpt3, a subunit of 26S proteasome with VAChT-Cre. Fast mice that displays motor neuron specific Cre expression. The motor neuron specific Rpt3 deficient mice showed tremor starting from 8 weeks of age and slowly progressive motor dysfunction from 12 weeks of age. Pathological findings revealed increased expression of the gene products of familial ALS such as FUS and TDP43, the latter forming cytoplasmic inclusion bodies. These results suggest that motor neuron-specific Rpt3 deficient mice represent a model for sporadic ALS.
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Report
(4 results)
Research Products
(92 results)
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[Journal Article] Nonhypotensive Dose of Telmisartan Attenuates Cognitive Impairment Partially due to Peroxisome Proliferator-Activated Receptor-γ Activation in Mice with Chronic Cerebral Hypoperfusion.2010
Author(s)
Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
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Journal Title
Stroke 41
Pages: 1798-1806
Related Report
Peer Reviewed
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[Journal Article] HtrA2/Omi-immunoreactive intraneuronal inclusions in the anterior horn from patients with sporadic and SOD1 mutant amyotrophic lateral sclerosis.2010
Author(s)
Kawamoto Y, Ito H, Kobayashi Y, Suzuki Y, Ihara M, Kawamata J, Akiguchi I, Fujimura H, Sakoda S, Kusaka H, Hirano A, Takahashi R
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Journal Title
Neuropath. Appl.Neurobiol. 36
Pages: 331-344
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Peer Reviewed
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[Journal Article] Negative motor seizure arising from the negative motor area : is it ictal apraxia?2009
Author(s)
Ikeda A, Hirasawa K, Kinoshita M, Hitomi T, Matsumoto R, Mitsueda T, Taki JY, Inouch M, Mikuni N, Hori T, Fukuyama H, Hashimoto N, Shibasaki H, Takahashi R
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Journal Title
Epilepsia. 50
Pages: 2072-2084
Related Report
Peer Reviewed
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[Journal Article] Diagnostic accuracy of cardiac metaiodobenzylguanidine scintigraphy in Parkinson disease.2009
Author(s)
Sawada H, Oeda T, Yamamoto K, Kitagawa N, Mizuta E, Hosokawa R, Ohba M, Nishio R, Yamakawa K, Takeuchi H, Shimohama S, Takahashi R, Kawamura T
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Journal Title
Eur J Neurol. 16
Pages: 174-182
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[Journal Article] N-cadherin-based adhesion enhances Abeta release and decreases Abeta42/40 ratio.2009
Author(s)
Uemura K, Lill CM, Banks M, Asada M, Aoyagi N, Ando K, Kubota M, Kihara T, Nishimoto T, Sugimoto H, Takahashi R, Hyman BT, Shimohama S, Berezovska O, Kinoshita A.
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Journal Title
J.Neurochem. 108
Pages: 350-360
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Peer Reviewed
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[Journal Article] Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models.2009
Author(s)
Takeuchi H, Yanagida T, Inden M, Takata K, Kitamura Y, Yamakawa K, Sawada H, Izumi Y, Yamamoto N, Kihara T, Uemura K, Inoue H, Taniguchi T, Akaike A, Takahashi R, Shimohama S
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Journal Title
J Neurosci Res. 87
Pages: 576-585
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Peer Reviewed
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[Journal Article] Parkin as a tumor suppressor gene for hepatocellular carcinoma.2008
Author(s)
Fujiwara M, Marusawa, H, Wang HQ, Iwai A, Ikeuchi K, Imai Y, Kataoka A, Nukina N, Takahashi R, Chiba T
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Journal Title
Oncogene. 27
Pages: 6002-6011
Related Report
Peer Reviewed
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