MECHANISMS OF UBIQUITIN LIGASE IN PATHOGENESIS OF ALZHEIMER'S DESEASE AND ABNORMAL NEURODIFFERNTIATION/DEVELOPMENTAL DISORDERE
| Project/Area Number |
24590119
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 小胞体ストレス / アルツハイマー病 / 神経分化 / 発達障害 / 神経幹細胞 |
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| Outline of Final Research Achievements |
The E3 ubiquitin ligase HRD1 is found in the endoplasmic reticulum membrane of brain neurons and is involved in endoplasmic reticulum-associated degradation. HRD1 levels are significantly decreased in the cerebral cortex of Alzheimer's disease patients because of its insolubility. The mechanisms were shown that HRD1 protein was insolubilized by oxidative stress. Thus, oxidative stress-induced HRD1 insolubilization might be involved in Alzheimer's disease pathogenesis.
Neural stem cells (NSCs) play an essential role in development of the central nervous system. Endoplasmic reticulum (ER) stress induces neuronal death. However, it is unclear whether ER stress directly affects neurogenesis-related processes such as neuronal differentiation and dendrite outgrowth. In the present study, ER stress caused aberrant neuronal differentiation from NSCs followed by the inhibition of neurite outgrowth. These events may be mediated by increased HRD1 expression.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that mimic 4-phenylbutyric acid.2015
Author(s)
Mimori S, Koshikawa Y, Mashima Y, Mitsunaga K, Kawada K, Kaneko M, Okuma Y, Nomura Y, Murakami Y, Kanzaki T, Hamana H.
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Journal Title
Bioorg Med Chem Lett.
Volume: 25
Issue: 4
Pages: 811-814
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Protective effects of 4-PBA derivatives on the neuronal cell death and endoplasmic reticulum stress.2012
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
Pages: 84-90
Related Report
Peer Reviewed
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[Journal Article] Effects of Hsp90 inhibitors, geldanamycin and its analog, on ceramide metabolism and cytotoxicity in PC12 cells.2012
Author(s)
Toyomura K, Saito T, Emori S, Matsumoto I, Kato E, Kaneko M, Okuma Y, Nakamura H, Murayama T.
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Journal Title
J Toxicol Sci.
Volume: 37
Pages: 1049-1057
Related Report
Peer Reviewed
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