2011 Fiscal Year Final Research Report
The inhibitory mechanism of unfolded protein accumulation in the endoplasmic reticulum : Studies on anti-neurodegeneration drug discovery
| Project/Area Number |
21300142
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Yokohama College of Pharmacy |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OKUMA Yasunobu 千葉科学大学, 薬学部, 教授 (20127939)
TAKAHASHI Ryosuke 京都大学, 大学院・医学研究科, 教授 (90216771)
KANEKO Masayuki 千葉科学大学, 薬学部, 准教授 (10322827)
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| Co-Investigator(Renkei-kenkyūsha) |
SHINOZUKA Tatsuo 横浜薬科大学, 薬学部, 准教授 (70095610)
IZUMO Nobuo 横浜薬科大学, 薬学部, 講師 (70368976)
TONOOKA Keiko 横浜薬科大学, 薬学部, 助教 (20521884)
HAMANA Hiroshi 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 | 神経変性疾患 / 小胞体ストレス / ERAD / ケミカルシャペロン / ユビキチンリガーゼ / 神経細胞死 / アルツハイマー病 / 酸化ストレス |
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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 found another ubiquitin ligase, which is involved in the amyloid β production. In addition, we synthesized some compounds, which prevent unfolded protein accumulation involved in Parkinson's disease.
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Research Products
(55 results)
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[Journal Article] Protective effects of 4-PBA(phenylbutyrate) 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. and Hamana, H.
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Journal Title
Biol. Pharm. Bull
Volume: 35
Pages: 84-90
Peer Reviewed
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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. and Okuma, Y.
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Journal Title
J. Pharmacol. Sci
Volume: 117
Pages: 208-212
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. and Nomura, Y.
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Journal Title
J. Neurosci
Volume: 30
Pages: 3924-3932
Peer Reviewed
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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
Peer Reviewed
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[Remarks] 新聞報道:(1)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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[Remarks] (2)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] (3)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1日掲載
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[Remarks] (4)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
