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Function of endoplasmic reticulum stress-related molecule, and effects of chemical chaperon involved in neurodegenerative disease

Research Project

Project/Area Number 19590073
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionChiba Institute of Science

Principal Investigator

OKUMA Yasunobu  Chiba Institute of Science, 薬学部, 教授 (20127939)

Co-Investigator(Kenkyū-buntansha) 浜名 洋  千葉科学大学, 薬学部, 教授 (00383472)
Co-Investigator(Renkei-kenkyūsha) 浜名 洋  千葉科学大学, 薬学部, 教授 (00383472)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords小胞体ストレス / ケミカルシャペロン / 細胞死 / パーキンソン病 / 神経変性疾患 / アルツハイマー病
Research Abstract

小胞体ストレスが関与する神経変性疾患との観点でユビキチンリガーゼの一種である新規遺伝子HRD1 はパーキンソン病で脱落が認められる黒質緻密層周辺のドパミンニューロンに発現していた。さらに、大脳皮質、海馬などにも発現していた。蛋白異常蛋白質の凝集を防ぐ働きを持つ化合物であるケミカルシャペロン4-PBA の誘導体および他の物質について、4-PBA と同等それ以上のケミカルシャペロン能を有する化合物が得られた。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (42 results)

All 2009 2008 2007

All Journal Article (19 results) (of which Peer Reviewed: 8 results) Presentation (23 results)

  • [Journal Article] Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain.2008

    • Author(s)
      Omura T, Kaneko M, Tabei N, Okuma Y, Nomura Y.
    • Journal Title

      J Neurosci Res 86(7)

      Pages: 1577-1587

    • Related Report
      2008 Final Research Report
  • [Journal Article] Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains.2008

    • Author(s)
      Omura T, Kaneko M, Onoguchi M, Koizumi S, Itami M, Ueyama M, Okuma Y, Nomura Y
    • Journal Title

      J Pharmacol Sci 106(3)

      Pages: 512-519

    • Related Report
      2008 Final Research Report
  • [Journal Article] Release of arachidonic acid induced by tumor necrosis factor-alpha in the presence of caspase inhibition: evidence for a cytosolic phospholipase A2alpha-independent pathway.2008

    • Author(s)
      Shimizu M, Matsumoto Y, Kurosawa T, Azuma C, Enomoto M, Nakamura H, Hirabayashi T, Kaneko M, Okuma Y, Murayama T.
    • Journal Title

      Biochem Pharmacol 75(6)

      Pages: 1358-1369

    • Related Report
      2008 Final Research Report
  • [Journal Article] Release of arachidonic acid by 2-arachidonoyl glycerol and HU210 in PC12 cells; roles of Src, phospholipase C and cytosolic phospholipase A(2)alpha.2008

    • Author(s)
      Nabemoto M, Mashimo M, Someya A, Nakamura H, Hirabayashi T, Fujino H, Kaneko M, Okuma Y, Saito T, Yamaguchi N, Murayama T
    • Journal Title

      Eur J Pharmacol 590(1-3)

      Pages: 1-11

    • Related Report
      2008 Final Research Report
  • [Journal Article] Vanadate inhibits endoplasmic reticulum stress responses.2008

    • Author(s)
      Hosoi T, Saito A, Kume A, Okuma Y, Nomura Y, Ozawa K.
    • Journal Title

      Eur J Pharmacol 594(1-3)

      Pages: 44-48

    • Related Report
      2008 Final Research Report
  • [Journal Article] Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain.2008

    • Author(s)
      Omura T, et al.
    • Journal Title

      Jounal of Neuroscience Research 86

      Pages: 1577-1587

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains.2008

    • Author(s)
      Omura T, et al.
    • Journal Title

      Journal of Pharmacological Science 106

      Pages: 512-519

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Release of arachidonic acid induced by tumor necrosis factor-alpha in the presence of caspase inhibition : evidence for a cytosolic phospholipase A2alpha-indeDendent pathway.2008

    • Author(s)
      Shimizu M, et al.
    • Journal Title

      Biochemical Pharmacology 75

      Pages: 1358-1369

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Release of arachidonic acid by 2-arachidonoyl glycerol and HU210 in PC12 cells ; roles of Src, phospholipase C and cytosolic phospholipase A(2)alpha.2008

    • Author(s)
      Nabemoto M, et al.
    • Journal Title

      European Jounal of Pharmacology 590

      Pages: 1-11

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vanadate inhibits endoplasmic reticulum stress responses.2008

    • Author(s)
      Hosoi T, et al.
    • Journal Title

      European Jounal of Pharmacology 594

      Pages: 44-48

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride on PI3K inhibitor-induced CHOP induction.2007

    • Author(s)
      Hosoi T, Hyoda K, Okuma Y, Nomura Y, Ozawa K.
    • Journal Title

      Eur J Pharmacol 554 (1)

      Pages: 8-11

    • Related Report
      2008 Final Research Report
  • [Journal Article] Geldanamycin induces CHOP expression through a 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF)-responsive serine protease.2007

    • Author(s)
      Hosoi T, Hyoda K, Okuma Y, Nomura Y, Ozawa K.
    • Journal Title

      Cell Res 17(2)

      Pages: 184-186

    • Related Report
      2008 Final Research Report
  • [Journal Article] Impairement of CREB phosphorylation in the hippocampal CA1 region of senescence-accelerated mouse (SAM) P8.2007

    • Author(s)
      Tomobe K, Okuma Y, Nomura Y.
    • Journal Title

      Brain Res 1141(1)

      Pages: 214-217

    • Related Report
      2008 Final Research Report
  • [Journal Article] Akt up- and down-regulation in response to endoplasmic reticulum stress.2007

    • Author(s)
      Hosoi T, Hyoda K, Okuma Y, Nomura Y, Ozawa K.
    • Journal Title

      Brain Res 1152(1)

      Pages: 27-31

    • Related Report
      2008 Final Research Report
  • [Journal Article] Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone.2007

    • Author(s)
      Inden M, Kitamura Y, Takeuchi H, Yanagida T, Takata K, Kobayashi Y, Taniguchi T, Yoshimoto K, Kaneko M, Okuma Y, Taira T, Ariga H, Shimohama S.
    • Journal Title

      J Neurochem 101(6)

      Pages: 1491-1504

    • Related Report
      2008 Final Research Report
  • [Journal Article] A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes.2007

    • Author(s)
      Kaneko M, Yasui S, Niinuma Y, Arai K, Omura T, Okuma Y, Nomura Y.
    • Journal Title

      FEBS Lett 581(28)

      Pages: 5355-5360

    • Related Report
      2008 Final Research Report
  • [Journal Article] Inhibitory effect of 4-(2-aminoethyl)-benzenesulfonyl fluoride on PI3Kinhibitor-induced CHOP induction2007

    • Author(s)
      Hosoi T, et. al.
    • Journal Title

      Eur J Pharmacol 554

      Pages: 8-11

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate,a chemical chaperone.2007

    • Author(s)
      Inden M, et. al.
    • Journal Title

      J Neurochem 101

      Pages: 1491-1504

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes2007

    • Author(s)
      Kaneko M, et. al.
    • Journal Title

      FEBS Lett 581

      Pages: 5355-5360

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 小胞体のユビキチンリガーゼHRD1の減少はAPPの蓄積とAβ産生増加を引き起こす2009

    • Author(s)
      金子雅幸、小池洋、齋藤僚、大熊康修、野村靖幸
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] HRD1 はユビキチンリガーゼ活性のみならず他の機能も有する蛋白質である2009

    • Author(s)
      大村友博、金子雅幸、小野口雅之、野村靖幸、大熊康修
    • Organizer
      第82 回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] 4-フェニル酪酸構造類似体の合成と解析2009

    • Author(s)
      三森盛亮、飯田博一、清水真希、金子雅幸、田窪裕介、齋藤弓子、池永枝里花、大村友博、大熊康修、浜名洋
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都市
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] アルツハイマー病患者脳におけるユビキチンリガーゼHRD1 タンパク質の減少2009

    • Author(s)
      齋藤僚、金子雅幸、野村靖幸、大熊康修
    • Organizer
      日本薬学会第129 年会
    • Place of Presentation
      京都市
    • Related Report
      2008 Final Research Report
  • [Presentation] HRD1はユビキチンリガーゼ活性のみならず他の機能も有する蛋白質である2009

    • Author(s)
      大村友博, 他
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Annual Research Report
  • [Presentation] ユビキチンリガーゼHRD1の膜貫通領域およびproline-rich領域の機能解析2008

    • Author(s)
      小野口雅之、大村友博、金子雅幸、大熊康修、野村靖幸
    • Organizer
      第119回日本薬理学会関東部会
    • Place of Presentation
      東京都
    • Year and Date
      2008-10-04
    • Related Report
      2008 Final Research Report
  • [Presentation] Suppression of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and β -amyloid generation with endoplasmic reticulum stress and apoptosis.2008

    • Author(s)
      M. Kaneko, T. Omura, H. Koike,Y. Okuma, Y. Nomura.
    • Organizer
      Society for Neuroscience 2008 Annual meeting.
    • Place of Presentation
      Washington D.C.
    • Related Report
      2008 Final Research Report
  • [Presentation] The brain distribution of a ubiquitin ligase HRD1 in mice.2008

    • Author(s)
      Y. Okuma, T. Omura, M. Kaneko, Y. Nomura.
    • Organizer
      Society for Neuroscience 2008 Annual meeting.
    • Place of Presentation
      Washington D.C.
    • Related Report
      2008 Final Research Report
  • [Presentation] ユビキチンリガーゼHRD1 の発現抑制はAPP の蓄積と小胞体ストレスによるアポトーシスを誘導する2008

    • Author(s)
      金子雅幸、小池洋、大村友博、大熊康修、野村靖幸
    • Organizer
      第81 回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] 小胞体ストレスの免疫機能に対する関与の可能性2008

    • Author(s)
      本多美那、細井徹、高桑美冴、大熊康修、野村靖幸、小澤光一郎
    • Organizer
      第81 回日本薬理学会年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] 4-フェニル酪酸構造類似体の合成とそのケミカルシャペロン活性の解析2008

    • Author(s)
      三森盛亮、飯田博一、五十嵐麻美子、浜名洋、金子雅幸、坪山沙有里、齋藤弓子、大村友博、大熊康修、松本澄
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] ユビキチンリガーゼHRD1のマウス脳内局在2008

    • Author(s)
      大村友博、金子雅幸、田部井直樹、大熊康修、野村靖幸
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] 小胞体関連分解ERADに関与するSEL1の脳内発現2008

    • Author(s)
      金子雅幸、井上慎也、大村友博、大熊康修1、野村靖幸
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] 利尿薬アミロライドが及ぼす小胞体ストレス応答への影響2008

    • Author(s)
      大谷芳代、細井徹、粂綾香、齊藤敦、大熊康修、野村靖幸、小澤光一郎
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] 新規小胞体ストレス関連遺伝子の同定および解析2008

    • Author(s)
      多武保泰治、細井徹、堀江直裕、大熊康修、野村靖幸、小澤光一郎
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report
  • [Presentation] HRD1のタンパク質分解抑制は小胞体ストレスとアポトーシスを伴うアミロイド前駆体タンパク質の蓄積とAβの産生増加を引き起こす2008

    • Author(s)
      金子雅幸、小池洋、大村友博1大熊康修、野村靖幸
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山市
    • Related Report
      2008 Final Research Report
  • [Presentation] The brain distribution of a ubiquitin ligase HRD1 in mice.2008

    • Author(s)
      Okuma Y, et al.
    • Organizer
      Society for Neuroscience 2008 Annual meeting
    • Place of Presentation
      Washington D. C.
    • Related Report
      2008 Annual Research Report
  • [Presentation] Suppression of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and β-amyloid generation with endoplasmic reticulum stress and apoptosis.2008

    • Author(s)
      Kaneko M, et al.
    • Organizer
      Society for Neuroscience 2008 Annual meeting
    • Place of Presentation
      Washington D. C.
    • Related Report
      2008 Annual Research Report
  • [Presentation] HRD1のタンパク質分解抑制は小胞体ストレスとアポトーシスを伴うアミロイド前駆体タンパク質の蓄積とA βの産生増加を引き起こす2008

    • Author(s)
      金子雅幸, 他
    • Organizer
      第51回日本神経化学会大会
    • Place of Presentation
      富山市
    • Related Report
      2008 Annual Research Report
  • [Presentation] Stress-induced Schlafen-8 Expression in the Brain2007

    • Author(s)
      L. Zhan, Y. Okuma, T. Hosoi,Y. Nomura.
    • Organizer
      The ASPN symposium supported by ISN on "Glial Activation and Fundtion"
    • Place of Presentation
      Dalian, China
    • Related Report
      2008 Final Research Report
  • [Presentation] 小胞体関連分解(ERAD )関連ユビキチンリガーゼHRD1 によるPael-受容体の分解機構の解析2007

    • Author(s)
      大村友博、金子雅幸、大熊康修、野村靖幸
    • Organizer
      第80 回日本薬理学会年会
    • Place of Presentation
      名古屋市
    • Related Report
      2008 Final Research Report
  • [Presentation] 小胞体の変性蛋白質分解関連分子HRD1 によるAPPの分解と神経細胞死抑制2007

    • Author(s)
      金子雅幸、大熊康修、野村靖幸
    • Organizer
      第34 回日本脳科学会
    • Place of Presentation
      出雲市
    • Related Report
      2008 Final Research Report
  • [Presentation] 小胞体関連分解ERAD に関するHRD1 はAPP によるアポトーシスを抑制する2007

    • Author(s)
      金子雅幸、小池洋、大村友博、大熊康修、野村靖幸
    • Organizer
      第50 回日神経化学会大会
    • Place of Presentation
      横浜市
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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