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Analysis of underlying mechanism to develop Alzheimer's disease

Research Project

Project/Area Number 23617007
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrated Nutrition Science
Research InstitutionGifu University

Principal Investigator

NAKAGAWA Toshiyuki  岐阜大学, 医学(系)研究科(研究院), 教授 (00271502)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords小胞体ストレス / ATF4 / GADD34 / eIF2alpha / アミロイドーベータ / eIF2α / アミロイド-β / PERK / GCN2 / アミロイドーβ / メタボリック症候群 / 肥満 / 糖尿病
Research Abstract

Gamma-secretase produces amyloid-beta (Ab) in the brain from Ab precursor protein, which is critical for tha pathogenesis of Alzheimer's disease (AD). The endoplasmic reticulum (ER) stress causes unfolded proteins, which are processed by unfolded protein response (UPR). Pathogenesis of obesity and diabetes, which are risk factors for AD, is related to ER stress. However, whether ER stress is engaged in the development of AD remains obscure. In this research, I showed that ER stress activated gamma-secretase, leading to augmentation of Ab through induction of activating transcription factor 4 (ATF4). Ab secretion was repressed in vitro by quercetin, which induced the growth arrest and DNA damaged-inducible gene (GADD)34. In addition, we found that phosphorylated eIF2alpha and ATF4 were increased in the brain of AD model mice APP23. These results suggest that ER stress signaling may be disturbed in the brain of AD.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 8 results) Presentation (11 results) Remarks (2 results)

  • [Journal Article] Polyglutamine expansion disturbs the endoplasmic reticulum formation, leading to caspase-7 activation through Bax2014

    • Author(s)
      M asashi Ueda, Shimo Li, Masanori Itoh, Yoshika Hayakawa-Yano, Miao-xing Wang, Miki Hayakawa, Ryoko Hasebe-Matsubara, Kazunori Ohta, Eri Ohta, Akihito Mizuno, Yoko Hida, Munekazu Matsumoto, Huayue Chen, Toshiyuki Nakagawa
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 443 Pages: 1232-1238

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Polyglutamine expansion disturbs the endoplasmic reticulum formation, leading to caspase-7 activation through Bax.2014

    • Author(s)
      Masashi Ueda, Shimo Li, Masanori Itoh, Yoshika Hayakawa-Yano, Miao-xing Wang, Miki Hayakawa, Ryoko Hasebe-Matsubara, Kazunori Ohta, Eri Ohta, Akihito Mizuno, Yoko Hida, Munekazu Matsumoto, Huayue Chen, Toshiyuki Nakagawa.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 443 Pages: 1232-1238

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning and sequence analysis of an extracellular protease from four bacillus strains2013

    • Author(s)
      Xujun Han, Yuh Shiwa, Masanori Itoh, Tohru Suzuki, Hirofumi Yoshikawa, Toshiyuki Nakagawa, Hiroko Nagano
    • Journal Title

      Biosci. Biotechnol. Biochem

      Volume: 77 Pages: 870-873

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular cloning and sequence analysis of an extracellular protease from four bacillus strains.2013

    • Author(s)
      Xujun Han, Yuh Shiwa, Masanori Itoh, Tohru Suzuki, Hirofumi Yoshikawa, Toshiyuki Nakagawa, Hiroko Nagano.
    • Journal Title

      Biosci. Biotechnol. Biochem.

      Volume: 77 Pages: 870-873

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Miao-xing Wang, ToshiyukiNakagawa. Olfaxin as a novel Prune2 isoform predominantly expressed in olfactory system2012

    • Author(s)
      Shimo Li, YoshikaHayakawa-Yano, MasanoriItoh, MasashiUeda, Kazunori Ohta, YoshihiroSuzuki, AkihitoMizuno, EriOhta, YokoHida
    • Journal Title

      Brain research

      Volume: 1488 Pages: 1-13

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Olfaxin as a novel Prune2 isoform predominantly expressed in olfactory system.2012

    • Author(s)
      Shimo Li,YoshikaHayakawa-Yano,MasanoriItoh,MasashiUeda, Kazunori Ohta,YoshihiroSuzuki,AkihitoMizuno,EriOhta,YokoHida, Miao-xing Wang,ToshiyukiNakagawa
    • Journal Title

      brain research

      Volume: 1488 Pages: 1-13

    • DOI

      10.1016/j.brainres.2012.10.001

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endoplasmic reticulum stress enhancesγ-secretase activity2011

    • Author(s)
      Ohta K, Mizuno A, Li S, Itoh M, Ueda M, Ohta E, Hida Y, Wang MX, Furoi M, Tsuzuki Y, Sobajima M, Bohmoto Y, Fukushima T, Kobori M, Inuzuka T, Nakagawa T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 416 Pages: 362-366

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 認知症2011

    • Author(s)
      太田和徳,中川敏幸
    • Journal Title

      Functional Food

      Volume: 5 Pages: 47-51

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Journal Article] ケルセチンとアルツハイマー病2011

    • Author(s)
      太田和徳,中川敏幸
    • Journal Title

      Functional Food

      Volume: 5 Pages: 135-138

    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Journal Article] Endoplasmic reticulum stress enhances γ-secretase activity.2011

    • Author(s)
      Ohta K, Mizuno A, Li S, Itoh M, Ueda M, Ohta E, Hida Y, Wang MX, Furoi M, Tsuzuki Y, Sobajima M, Bohmoto Y, Fukushima T, Kobori M, Inuzuka T, Nakagawa T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 416 Issue: 3-4 Pages: 362-366

    • DOI

      10.1016/j.bbrc.2011.11.042

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] CUL4B PROMOTES APAF-1 POLYYUBIQUITINATION FOR CASPASE-9 ACTIVATION2013

    • Author(s)
      Masanori Itoh, Eri Ohta, Yoko Hida, Miao-xing Wang, Masashi Ueda, Kazunori Ohta, Shimo Li, Akihito Mizuno, Tomomi Sunayama, Toshiyuki Nakagawa
    • Organizer
      Cold Spring Harbor Asia
    • Place of Presentation
      Suzhou(宿州)China
    • Year and Date
      2013-04-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Activation of gamma-secretase by endoplasmic reticurum stress2012

    • Author(s)
      Kazunori Ohta, Akihito Mizuno, Shimo Li, Masanori Itoh, Masashi Ueda, Yoko Hida, Miao-xing Wang, Wan-yu Lo, Toshiyuki Nakagawa
    • Organizer
      42nd ANNUAL MEETING Neuroscience
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2012-10-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Endoplasmic reticulum stress leads to increase gamma-secretase activity and beta-amyloid production2011

    • Author(s)
      Kazunori Ohta, Akihito Mizuno, Shimo Li, Masashi Ueda, Masanori Itoh, Eri Ohta, Yoko Hida, Miao-xing Wang , Manabu Furoi, Yukihiro Tuzuki, Mituaki Sobajima, Yoshimasa Bohmoto, Tatsuya Fukushima, Toshituki Nakagawa
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜(3P-701)
    • Year and Date
      2011-12-15
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel regulation mechanism of synaptic transmission by preseynapse-localizing Caymanataxia-related protein,Caytaxin2011

    • Author(s)
      Masanori itoh, Shimo Li, Kazunori Ohta, Masashi Ueda, Yoko Hida, Yoshihiro Suzuki, Eri Ohta, Akihito Mizuno, Miao-xing Wang, Toshiyuki Nakagawa
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜(1P-0921)
    • Year and Date
      2011-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] The expression and localization of Prune2 and its novel isoform in the central neuvous system2011

    • Author(s)
      S.LI, M.ITOH, K.OHTA, M.UEDA, A.MIZUNO, E.OHTA, Y.HIDA, M.WANG, K.YAKEUCHI, T.NAKAGAWA
    • Organizer
      41th ANNUAL MEETING Neuroscience2011
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Endoplasmic reticulum stress leads to increase gamma-secretase activity and beta-amyloid production2011

    • Author(s)
      K. Ohta, A. Mizuno, S. Li, M. Ueda, M. Itoh, E. Ohta, Y. Hida, M. Wang , M. Furoi, Y. Tuzuki, M. Sobajima, Y. Bohmoto, T. Fukushima, T. Nakagawa
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] A novel regulation mechanism of synaptic transmission by preseynapse-localizing Caymanataxia-related protein,Caytaxin2011

    • Author(s)
      M. itoh, S. Li, K. Ohta, M. Ueda, Y. Hida, Y. Suzuki, E. Ohta, A. Mizuno, M. Wang, T. Nakagawa
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] The expression and localization of Prune2 and its novel isoform in the central neuvous system2011

    • Author(s)
      S.LI, M.ITOH, K.OHTA, M.UEDA, A.MIZUNO, E.OHTA, Y.HIDA, M.WANG, K.YAKEUCHI, T.NAKAGAWA
    • Organizer
      41thANNUAL MEETING Neuroscience
    • Place of Presentation
      Washington DC, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] CUL4B PROMOTES APAF-1 POLYYUBIQUITINATION FOR CASPASE-9 ACTIVATION.

    • Author(s)
      Masanori Itoh, Eri Ohta, Yoko Hida, Miao-xing Wang, Masashi Ueda, Kazunori Ohta, Shimo Li, Akihito Mizuno, Tomomi Sunayama, Toshiyuki Nakagawa.
    • Organizer
      Cold Spring Harbor Asia.
    • Place of Presentation
      Suzhou(宿州) China
    • Related Report
      2013 Annual Research Report
  • [Presentation] Polyglutamine expansion affects morphology of the endoplasmic reticulum-mitochondria contact site, initiating cell death.

    • Author(s)
      Masashi Ueda, Shimo Li, Masanori Itoh, Kazunori Ohta, Miao-xing Wang, Huayue Chen, K.Yamaguchi, K. Kuwata, Miki Hayakawa, Yoko Hida, Toshiyuki Nakagawa.
    • Organizer
      43rd ANNUAL MEETING Neuroscience.
    • Place of Presentation
      San Diego, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Activation of gamma-secretase by endoplasmic reticurum stress.

    • Author(s)
      Kazunori Ohta, Akihito Mizuno, Shimo Li, Masanori Itoh, Masashi Ueda, Yoko Hida, Miao-xing Wang, Wan-yu Lo, Toshiyuki Nakagawa.
    • Organizer
      42nd ANNUAL MEETING Neuroscience
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www1.gifu-u.ac.jp/~neurobio/

    • Related Report
      2013 Final Research Report
  • [Remarks] http://www1.gifu-u.ac.jp/~neurobio/

    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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