• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The inhibitory mechanism of novel proteins induced in the endoplasmic reticulum and of drugs on neurodegenerative diseases

Research Project

Project/Area Number 19300135
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionYokohama College of Pharmacy

Principal Investigator

NOMURA Yasuyuki  Yokohama College of Pharmacy, 薬学部, 教授 (00034041)

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)
UEHARA Takashi  北海道大学, 大学院・薬学研究院, 准教授 (00261321)
KANEKO Masayuki  千葉科学大, 薬学部, 講師 (10322827)
IZUMO Nobuo  横浜薬科大学, 薬学部, 講師 (70368976)
ISUZUGAWA Kazuto  横浜薬科大学, 薬学部, 講師 (90412551)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2007: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywords小胞体 / 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 / 構造活性相関 / APP / ユビキチン / プロテアソーム
Research Abstract

本研究では,抗脳神経変性疾患薬創製に向けて, 細胞内小器官小胞体への変性タンパク質蓄積抑制機構に関する研究を行った. 小胞体のタンパク質分解系(ERAD)分子の生体での生理的役割, とくに脳変性疾患への関与を明らかにするとともに, ERAD 分子をターゲットとした脳変性疾患抑制薬の基盤研究を行った. また, タンパク質凝集抑制作用を有する化合物を作成し, 神経細胞死抑制作用について検討した.

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 (18 results) (of which Peer Reviewed: 18 results) Presentation (23 results) Book (1 results)

  • [Journal Article] Neurochemistry, neuropathology, and heredity in SAMP8: a mouse model of senescence2009

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

      Neurochem Res. 34

      Pages: 660-669

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neurochemistry, neuropathology, and heredity in SAMP8 : a mouse model of senescence2009

    • Author(s)
      Tomobe, K.
    • Journal Title

      Neurochem. Res. 34

      Pages: 660-669

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains2008

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

      J. Pharmacol. Sci. 106

      Pages: 512-519

    • NAID

      10024319569

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain2008

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

      J. Neurosci. Res. 86

      Pages: 1577-1587

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vanadate inhibits endoplasmic reticulum stress responses2008

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

      Eur J Pharmacol 594

      Pages: 44-48

    • NAID

      120001092429

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] GMEB1, a novel endogenous caspase inhibitor2008

    • Author(s)
      Nakagawa, T., Tsuruma, K., Uehara, T. and Nomura, Y
    • Journal Title

      prevents hypoxia- and oxidative stress-induced neuronal apoptosis, Neurosci Lett 438

      Pages: 34-37

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain2008

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

      J. Pharmacol. Sci. 106

      Pages: 512-519

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vanadate inhibits endoplasmic reticulum stress responses2008

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

      Eur. J. Pharmacol. 594

      Pages: 44-48

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GMEB1, a novel endogenous caspase inhibitor, prevents hypoxia-and oxidative stress-induced neuronal apoptosis2008

    • Author(s)
      Nakagawa, T.
    • Journal Title

      Neurosci. Lett. 438

      Pages: 34-37

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical localization of a ubiquitin ligase HRD1 in murine brain2008

    • Author(s)
      T. Omura
    • Journal Title

      J Neurosci Res 86

      Pages: 1577-87

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains2008

    • Author(s)
      T. Omura
    • Journal Title

      J Pharmacol Sci 106

      Pages: 512-9

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GMEB1, a novel endogenous caspase inhibitor, prevents hypoxia-and oxidative stress-induced neuronal apoptosis2008

    • Author(s)
      T. Nakagawa
    • Journal Title

      Neurosci Lett (印刷中)

    • 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., Yasui, S., Niinuma, Y., Arai, K., Omura, T., Okuma, Y. and Nomura, Y.
    • Journal Title

      FEBS Lett. 581

      Pages: 5355-5360

    • NAID

      120000951780

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of CREB phosphorylation in the hippocampal CA1 region of the senescence-accelerated mouse (SAM) P82007

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

      Brain Res. 1141

      Pages: 214-217

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes2007

    • Author(s)
      M. Kaneko
    • Journal Title

      FEBS Lett 581

      Pages: 5355-60

    • NAID

      120000951780

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of misfolded protein through nitrosative stress linked to neurodegenerative disorders2007

    • Author(s)
      T. Uehara
    • Journal Title

      Antioxid Redox Signal 9

      Pages: 597-601

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt up-and down-regulation in response to endoplasmic reticulum stress2007

    • Author(s)
      T. Hosoi
    • Journal Title

      Brain Res 1152

      Pages: 27-31

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of CREB phosphorylation in the hippocampal CA1 region of the senescence-accelerated mouse(SAM)P82007

    • Author(s)
      K. Tomobe
    • Journal Title

      Brain Res 1141

      Pages: 214-7

    • 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の産生増加を引き起こす2009

    • Author(s)
      金子 雅幸
    • Organizer
      第82回日本薬理学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-18
    • 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2009

    • Author(s)
      大村 友博
    • Organizer
      第82回日本薬理学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒト新規小胞体タンパク質HRD1の神経変性疾患治療に関する薬理学的基盤研究(第24回日本薬理学会学術奨励賞受賞講演)2009

    • Author(s)
      金子 雅幸
    • Organizer
      第82回日本薬理学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒト新規小胞体タンパク質HRD1の神経変性疾患治療に関する薬理学的基盤研究2009

    • Author(s)
      金子雅幸
    • Organizer
      第82回日本薬理学会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [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の産生増加を引き起こす2009

    • Author(s)
      金子雅幸, 小池洋, 齋藤僚, 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
    • Related Report
      2008 Final 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
    • Related 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
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] The brain distribution of a ubiquitin ligase HRD1 in mice2008

    • Author(s)
      Okuma, Y.
    • Organizer
      Neuroscience 2008
    • Place of Presentation
      Washington, D. C.
    • Year and Date
      2008-11-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Suppression of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and ss-amyloid generation with endoplasmic reticulum stress and apoptosis2008

    • Author(s)
      Kaneko, M.
    • Organizer
      Neuroscience 2008
    • Place of Presentation
      Washington, D. C.
    • Year and Date
      2008-11-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] HRD1の発現抑制によるAPPの分解阻害はAβ産生増加と小胞体ストレスを誘発する2008

    • Author(s)
      金子 雅幸
    • Organizer
      第35回日本脳科学会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-13
    • Related Report
      2008 Annual 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
    • Related Report
      2008 Final Research Report 2007 Annual 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, 野村靖幸
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • 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
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] 4-フェニル酪酸構造類似体の合成による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, 大村友博, 金子雅幸, 大熊康修, 松本澄
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] HRD1の発現抑制によるAPP の分解阻害はAβ産生増加と小胞体ストレスを誘発する2008

    • Author(s)
      金子雅幸, 大熊康修, 野村靖幸
    • Organizer
      第35回日本脳科学会
    • Place of Presentation
      東京
    • 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, 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
    • Related Report
      2008 Annual Research Report 2008 Final 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
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Suppression of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and b-amyloid generation with endoplasmic reticulum stress and apoptosis2008

    • Author(s)
      Kaneko, M., Koike, H., Omura, T., Okuma, Y. and Nomura, Y.
    • Organizer
      Neuroscience 2008
    • Place of Presentation
      Washington, DC
    • Related Report
      2008 Final Research Report
  • [Presentation] The brain distribution of a ubiquitin ligase HRD1 in mice2008

    • Author(s)
      Okuma, Y., Omura, T., Kaneko, M. and Nomura, Y.
    • Organizer
      Neuroscience 2008
    • Place of Presentation
      Washington, DC
    • Related Report
      2008 Final Research Report
  • [Presentation] 4・フェニル酪酸構造類似体の合成によるケミカルシャペロン活性の解析2008

    • Author(s)
      三森盛亮
    • Organizer
      日本薬学会第128年会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 小胞体の変性タンパク質分解関連分子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
    • Related Report
      2008 Final Research Report
  • [Presentation] 小胞体関連分解ERADに関与するHRD1はAPPによるアポトーシス抑制する2007

    • Author(s)
      金子雅幸, 小池洋, 大村友博, 大熊康修, 野村靖幸
    • Organizer
      Neuro2007(第50回日本神経化学会大会)
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report 2007 Annual 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
    • Organizer
      第34回日本脳科学会
    • Place of Presentation
      出雲
    • Related Report
      2007 Annual Research Report
  • [Book] 機能形態学(機能形態学総論)2008

    • Author(s)
      野村 靖幸
    • Total Pages
      15
    • Publisher
      化学同人
    • Related Report
      2008 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi