2010 Fiscal Year Final Research Report
Possible involvement of endoplasmic reticulum protein degradation in Alzheimer's disease
| Project/Area Number |
21790089
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Chiba Institute of Science |
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Principal Investigator |
KANEKO Masayuki Chiba Institute of Science, 薬学部, 講師 (10322827)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 小胞体ストレス / ERAD / アルツハイマー病 / ユビキチンリガーゼ / APP / 小胞体 / ニューロン / 神経変性疾患 |
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| Research Abstract |
HRD1 promotes degradation of unfolded proteins in the endoplasmic reticulum as a ubiquitin ligase. In the present study, we suggest the possible involvement of oxidative stresses in the decrease of HRD1 protein, which promotes degradation of amyloid precursor protein (APP), in the brain of Alzheimer's disease (AD) patient. Furthermore, we evaluated whether HRD1 knockout mice exhibited the phenotypes of AD. In addition, we found another ubiquitin ligase, which is involved in the APP protein metabolism.
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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., Murayama, T.
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Journal Title
J.Pharmacol.Sci. 114
Pages: 420-432
Peer Reviewed
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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., Nomura, Y.
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Journal Title
J.Neurosci. 30
Pages: 3924-3932
Peer Reviewed
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[Remarks] 新聞報道:
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[Remarks] 読売新聞夕刊(9面)「アルツハイマー患者発症防ぐ酵素半分」,2010年7月7日掲載
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[Remarks] 神奈川新聞朝刊(23面)「認知症予防に光明酵素ヒトHRD1発見」,2010年7月1日掲載
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[Remarks] 薬事日報(3面)「HRD1がAβ分解に関与アルツハイマー病治療に期待」,2010年5月21日掲載
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[Remarks] 科学新聞(4面)「アルツハイマー病発症脳タンパク質HRD1が関与患者の死後脳で減少」,2010年4月16日掲載
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