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A novel trafficking mechanism regulated by bisecting GlcNAc, an Alzheimer's disease accelerator

Research Project

Project/Area Number 26670148
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Kizuka Yasuhiko  国立研究開発法人理化学研究所, 疾患糖鎖研究チーム, 研究員 (20564743)

Research Collaborator SATO Keiko  国立研究開発法人理化学研究所, 疾患糖鎖研究チーム, パートタイマー
KITAZUME Shinobu  国立研究開発法人理化学研究所, 疾患糖鎖研究チーム, 副チームリーダー (80301753)
TANIGUCHI Naoyuki  国立研究開発法人理化学研究所, システム糖鎖生物学研究グループ, グループディレクター (90002188)
NAKANO Miyako  広島大学, 先端物質科学研究科, 准教授 (40397724)
NAKAJIMA Kazuki  藤田保健衛生大学, 研究支援推進センター, 講師 (10442998)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords糖鎖 / アルツハイマー病 / BACE1 / バイセクト糖鎖 / GnT-III
Outline of Final Research Achievements

The aim of this study is to clarify the mechanisms of Alzheimer's disease (AD) development, focusing on a neural glycan bisecting GlcNAc.
We focused on AD-related protein BACE1 and identified its new interacting partner Clec4g. Furthermore, our data suggest that oxidative stress induced in AD brain upregulates the level of bisecting GlcNAc on BACE1, which could lead to AD development. These findings will be useful to better understand the mechanisms of AD development.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results)

  • [Int'l Joint Research] Academia Sinica(台湾)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Saarland University(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Expression of Neural Glycans and Their Role in Disease2017

    • Author(s)
      Kizuka Y.
    • Journal Title

      Trends in Glycoscience and Glycotechnology

      Volume: 29 Issue: 165 Pages: E11-E18

    • DOI

      10.4052/tigg.1613.2E

    • NAID

      130005297139

    • ISSN
      0915-7352, 1883-2113
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery.2016

    • Author(s)
      Kizuka Y, Funayama S, Shogomori H, Nakano M, Nakajima K, Oka R, Kitazume S, Yamaguchi Y, Sano M, Korekane H, Hsu TL, Lee HY, Wong CH, Taniguchi N.
    • Journal Title

      Cell Chemical Biology

      Volume: 23 Issue: 7 Pages: 782-792

    • DOI

      10.1016/j.chembiol.2016.06.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Epigenetic regulation of neural N-glycomics.2016

    • Author(s)
      Kizuka Y, Nakano M, Miura Y, Taniguchi N.
    • Journal Title

      Proteomics

      Volume: 16 Issue: 22 Pages: 2854-2863

    • DOI

      10.1002/pmic.201600053

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Disease-associated glycans on cell surface proteins.2016

    • Author(s)
      Takahashi M, Kizuka Y, Ohtsubo K, Gu J, Taniguchi N.
    • Journal Title

      Molecular Aspects of Medicine

      Volume: 51 Pages: 56-70

    • DOI

      10.1016/j.mam.2016.04.008

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enzymes for N-Glycan Branching and Their Genetic and Nongenetic Regulation in Cancer.2016

    • Author(s)
      Kizuka Y, Taniguchi N.
    • Journal Title

      Biomolecules

      Volume: 6 Issue: 2 Pages: 25-25

    • DOI

      10.3390/biom6020025

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Bisecting GlcNAc modification stabilizes BACE1 protein under oxidative stress conditions2016

    • Author(s)
      Kizuka Y, Nakano M, Kitazume S, Saito T, Saido TC, Taniguchi N
    • Journal Title

      Biochemical Journal

      Volume: 473 Issue: 1 Pages: 21-30

    • DOI

      10.1042/bj20150607

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clec4g (LSECtin) interacts with BACE1 and suppresses Aβ generation2015

    • Author(s)
      Kizuka Y, Kitazume S, Sato K, Taniguchi N
    • Journal Title

      FEBS Letters

      Volume: 589 Issue: 13 Pages: 1418-1422

    • DOI

      10.1016/j.febslet.2015.04.060

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of N-glycans in cancer biomarker, progression and metastasis and therapeutics2015

    • Author(s)
      Naoyuki Taniguchi, Yasuhiko Kizuka
    • Journal Title

      Advances in Cancer Research

      Volume: 126 Pages: 11-51

    • DOI

      10.1016/bs.acr.2014.11.001

    • Related Report
      2014 Research-status Report
  • [Presentation] 神経系における糖鎖修飾とアルツハイマー病2017

    • Author(s)
      木塚康彦
    • Organizer
      第13回レドックス・ライフイノベーションシンポジウム
    • Place of Presentation
      奈良女子大学(奈良)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病におけるbisecting GlcNAc糖鎖の役割について2017

    • Author(s)
      木塚康彦
    • Organizer
      新学術領域「神経糖鎖生物学」最終シンポジウム
    • Place of Presentation
      JPタワー(名古屋)
    • Year and Date
      2017-03-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Bisecting GlcNAc糖鎖修飾とアルツハイマー病に関する研究2016

    • Author(s)
      木塚康彦、北爪しのぶ、谷口直之
    • Organizer
      第57回日本生化学会 中国・四国支部例会
    • Place of Presentation
      高知大学(高知)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Glyco-redox, a link of glycobiology and redox balance, is implicated in Alzheimer’s disease2016

    • Author(s)
      Kizuka Y., Chienwichai P., Taniguchi N
    • Organizer
      The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Place of Presentation
      仙台国際センター(仙台)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Physiological and pathological roles of bisecting GlcNAc2016

    • Author(s)
      Kizuka Y., Nakano M., Kitazume S., Taniguchi N.
    • Organizer
      RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, The fifth symposium
    • Place of Presentation
      ベルリン(ドイツ)
    • Year and Date
      2016-04-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルツハイマー病を促進させるバイセクト糖鎖2016

    • Author(s)
      木塚康彦、北爪しのぶ、谷口直之
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] BACE1のbisecting GlcNAc修飾によるアルツハイマー病の発症メカニズム2015

    • Author(s)
      木塚康彦、北爪しのぶ、中の三弥子、西道隆臣、橋本康弘、遠藤玉夫、谷口直之
    • Organizer
      第88回日本生化学会大会 第38回日本分子生物学会年会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Bisecting GlcNAcによるBACE1の分解制御メカニズム2015

    • Author(s)
      木塚康彦、中の三弥子、北爪しのぶ、斉藤貴志、西道隆臣、谷口直之
    • Organizer
      GlycoTOKYO2015シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2015-10-24
    • Related Report
      2015 Research-status Report
  • [Presentation] Bisecting GlcNAc on BACE1 is a Novel Therapeutic Target for Alzheimer’s Disease2015

    • Author(s)
      Kizuka Y, Kitazume S, Nakano M, Saido T, Hashimoto Y, Endo T, Taniguchi N
    • Organizer
      XXIII International Symposium on Glycoconjugates.
    • Place of Presentation
      Split (Croatia)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bisecting GlcNAc regulates Alzheimer’s Disease development2015

    • Author(s)
      Kizuka Y, Kitazume S, Nakano M, Saido T, Yamaguchi Y, Yoshida M, Hashimoto Y, Endo T, Taniguchi N
    • Organizer
      4th Austria-Japan Seminar for Comparative and Developmental Glycobiology
    • Place of Presentation
      Split (Croatia)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経系糖鎖の発現制御と認知症病態形成における役割についての研究2015

    • Author(s)
      木塚康彦
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Bisecting GlcNAcは酸化ストレスによるBACE1の発現誘導を制御する2015

    • Author(s)
      木塚康彦、北爪しのぶ、谷口直之
    • Organizer
      第2回FCCAシンポジウムFCCAグライコサイエンス若手フォーラム2015
    • Place of Presentation
      東京
    • Year and Date
      2015-07-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Bisecting GlcNAc modification is a novel therapeutic target for Alzheimer’s disease2015

    • Author(s)
      Kizuka Y, Kitazume S, Saido T, Nakano M, Ohnuki T, Shirouzu M, Yoshida M, Zegzouti H, Endo T, Taniguchi N
    • Organizer
      RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, The 4th symposium
    • Place of Presentation
      神戸
    • Year and Date
      2015-05-11
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] High-throughput screening of GnT-III inhibitors using UDP-Glo system to develop a novel drug candidate for Alzheimer’s disease2014

    • Author(s)
      Yasuhiko Kizuka, Shinobu Kitazume, Keiko Sato, Tetsuo Ohnuki, Mutsuko Kukimoto-Niino, Mikako Shirouzu, Minoru Yoshida, Laurie Engel, Hicham Zegzouti, Naoyuki Taniguchi
    • Organizer
      SFG & JSCR 2014 Joint Annual Meeting
    • Place of Presentation
      Honolulu
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] Bisecting GlcNAc欠損によるアルツハイマー病抑制に関する研究2014

    • Author(s)
      木塚康彦、北爪しのぶ、藤縄玲子、斎藤貴志、岩田修永、西道隆臣、中の三弥子、山口芳樹、橋本康弘、Matthias Staufenbiel、初田裕幸、村山繁雄、萬谷博、遠藤玉夫、谷口直之
    • Organizer
      第33回日本糖質学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-08-10 – 2014-08-12
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2022-02-16  

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