2011 Fiscal Year Final Research Report
DEGRADATION OF ABNORMAL PROTEIN/ANTIAGRIGATION SUBSTANCE, REGARDING ENDOPLASMIC RETICULUM ASSOCIATED MOLECULE AS A TARGET OF THERAPEUTIC AGENT ON NEURODEGERERATIVE DISEASE
| Project/Area Number |
21590101
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Chiba Institute of Science |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
浜名 洋 千葉科学大学, 薬学部, 教授 (00383472)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 小胞体ストレス / ケミカルシャペロン / 細胞死 / アルツハイマー病 / パーキンソン病 / 神経変性疾患 |
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| Research Abstract |
The ubiquitin ligase(E3) HRD1 protein levels were significantly decreased in the cerebral cortex of patients with Alzheimer's disease(AD), and that the brains of these patients were under ER stress. Furthermore, HRD1 levels negatively correlated with Aβlevels. The present study revealed that the decrease in HRD1 levels was due to its insolubilization. A reactive oxygen species(ROS)-induced insolubilization of HRD1 and SEL1L may be involved in Aβgeneration in the pathogenesis of AD. Neural stem/progenitor cells(NSCs) reside in the subventricular zone(SVZ) and subgranular zone of the hippocampal dentate gyrus in adult mammals. We found the localization of HRD1 in the NSCs of the adult brain. We found that several 4-phenylbutyric acid 1(4-PBA) derivatives demonstrated anti-aggregation activity as a chemical chaperone activity higher than that of 4-PBA.
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Research Products
(44 results)
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[Journal Article] Protective effects of 4-PBA derivatives on the neuronal cell death and endoplasmic reticulum stress2012
Author(s)
Mimori, S, Okuma Y., Kaneko M, Kawada, K Hosoi, T, Ozawa, K, Nomura Y, Hamada H
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Journal Title
Biol. Pharm. Bull
Volume: 35(1)
Pages: 84-90
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[Journal Article] Expression of the Ubiquitin Ligase HRD1 in Neural Stem/Progenitor Cells of the Adult Mouse Brain2011
Author(s)
Kawada K, Kaneko, M, Nomura Y, Mimori, S, Hamana, H, Ogita, K, Murayama, T, Fujino, H, Okuma Y
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Journal Title
J. Pharmacol. Sci
Volume: 117(3)
Pages: 208-12
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[Journal Article] Loss of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and amyloid-beta generation2010
Author(s)
Kaneko, M., Koike, H., Saito, R., Kitamura, Y., Okuma, Y. and Nomura, Y
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Journal Title
J. Neurosci.
Volume: 30
Pages: 3924-3932
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[Journal Article] Activation of ceramidase and ceramide kinase by vanadate via a tyrosine kinase-mediated pathway2010
Author(s)
Tada, E., Toyomura, K., Nakamura, H., Sasaki, H., Saito, T., Kaneko, M., Okuma, Y. and Murayama, T
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Journal Title
J. Pharmacol. Sci.
Volume: 114
Pages: 420-432
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