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The role of abnormal alpha-synuclein and its partners in synucleinopathy

Research Project

Project/Area Number 23500425
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionHirosaki University

Principal Investigator

TANJI kunikazu  弘前大学, 医学(系)研究科(研究院), 助教 (10271800)

Co-Investigator(Kenkyū-buntansha) WAKABAYASHI Koichi  弘前大学, 大学院・医学研究科, 教授 (50240768)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsタンパク質分解 / 異常蓄積 / 神経変性 / 神経変性疾患 / アルツハイマー病 / パーキンソン病 / レビー小体型認知症 / シナプス / 封入体 / ユビキチン / プロテアソーム / オートファジー
Research Abstract

Abnormal synuclein is deposited in the presynapses and cytoplasmic inclusions found in synucleinopathy such as Parkinsons disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy. Likewise, NUB1 is also accumulated in these specific regions together with abnormal synuclein. Although NUB1 can degrade synuclein expressed in cultured cells, it is not clear that NUB1 possesses this ability in vivo. We created transgenic mice expressing NUB1 and synuclein to investigate the role of NUB1 on abnormal synuclein deposition. Immunohistochemical and biochemical studies confirmed that NUB1 was expressed in the neurons. Unexpectedly, however, there were no alterations of abnormal synuclein deposition between mice expressing synuclein and synuclein/NUB1. These results suggest that NUB1 unlikely degrades synuclein in vivo.

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 (11 results) (of which Peer Reviewed: 11 results,  Open Access: 2 results) Presentation (9 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Accumulation of the sigma-1 receptor is common to neuronal nuclear inclusions in various neurodegenerative diseases.2014

    • Author(s)
      Miki Y, Mori F, Kon T, Tanji K, Toyoshima Y, Yoshida M, Sasaki H, Kakita A, Takahashi H, Wakabayashi K.
    • Journal Title

      Neuropathology

      Volume: 34 Issue: 2 Pages: 148-158

    • DOI

      10.1111/neup.12080

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Carnosic acid suppresses the production of amyloid-beta 1-42 and 1-43 by inducing an alpha-secretase TACE/ADAM17 in U373MG human astrocytoma cells.2014

    • Author(s)
      Yoshida H, Meng P, Matsumiya T, Tanji K, Hayakari R, Xing F, Wang L, Tsuruga K, Tanaka H, Mimura J, Kosaka K, Itoh K, Takahashi I, Imaizumi T
    • Journal Title

      Neurosci Res

      Volume: 79 Pages: 89-94

    • DOI

      10.1016/j.neures.2013.11.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ALS-associated protein FIG4 is localized in Pick and Lewy bodies, and neuronal nuclear inclusions in polyglutamine and intranuclear inclusion body diseases.2014

    • Author(s)
      Kon T, Mori F, Yanji F, Miki Y, Toyoshima Y, Yoshida M, Sasaki H, Kakita A, Takahashi H, Wakabayashi K
    • Journal Title

      Neuropathology

      Volume: 34 Issue: 1 Pages: 19-26

    • DOI

      10.1111/neup.12056

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FUS colocalizes with polyglutamine, but not with TDP-43 in neuronal intranuclear inclusions in spinocerebellar ataxia type 2.2014

    • Author(s)
      Mori F, Toyoshima Y, Tanji K, Kakita A, Takahashi H, Wakabayashi K.
    • Journal Title

      Neuropathol Appl Neurobiol

      Volume: 40 Issue: 3 Pages: 351-355

    • DOI

      10.1111/nan.12075

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases2013

    • Author(s)
      Tanji K, Maruyama A, Odagiri S, Mori F, Itoh K, Kakita A, Takahashi H, Wakabayashi K
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 72 Issue: 1 Pages: 18-28

    • DOI

      10.1097/nen.0b013e31827b5713

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Brain expression level and activity of HDAC6 protein in neurodegenerative dementia.2013

    • Author(s)
      Odagiri S, Tanji K, Mori F, Miki Y, Kakita A, Takahashi H, Wakabayashi K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 430 Issue: 1 Pages: 397-399

    • DOI

      10.1016/j.bbrc.2012.11.034

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The lewy body in Parkinson's disease and related neurodegenerative disorders.2013

    • Author(s)
      Wakabayashi K, Tanji K, Odagiri S, Miki Y, Mori F, Takahashi H.
    • Journal Title

      Mol. Neurobiol.

      Volume: 47 Issue: 2 Pages: 495-508

    • DOI

      10.1007/s12035-012-8280-y

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] p62/sequestosome 1 binds to TDP-43 in the brains of frontotemporal lobar degeneration with TDP-43 inclusions2012

    • Author(s)
      Tanji K, et al.
    • Journal Title

      J Neurosci Res

      Volume: 90(印刷中) Issue: 10 Pages: 2034-2042

    • DOI

      10.1002/jnr.23081

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alteration of autophagosomal proteins in the brain of multiple system atrophy.2012

    • Author(s)
      Tanji K, Odagiri S, Maruyama A, Mori F, Kakita A, Takahashi H, Wakabayashi K.
    • Journal Title

      Neurobiol Dis

      Volume: 49C Pages: 190-198

    • DOI

      10.1016/j.nbd.2012.08.017

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autophagic adapter protein NBR1 is localized in Lewy bodies and glial cytoplasmic inclusions and is involved in aggregate formation in α-synucleinopathy2012

    • Author(s)
      Odagiri S, Tanji K, Mori F, Kakita A, Takahashi H, Wakabayashi K.
    • Journal Title

      Acta Neuropathol

      Volume: (in press) Issue: 2 Pages: 173-186

    • DOI

      10.1007/s00401-012-0975-7

    • NAID

      110009614141

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Syinpilin 1-binding protein NUB1 is colocalized with nonfibrillar, proteinase K-resistant・-synuclein in presynapses in Lewy Body disease2011

    • Author(s)
      Tanji K, Mori F, Kito K, Kakita A, Mimura J, Itoh K, Takahashi H, Kamitani T, Wakabayashi K
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 70 Issue: 10 Pages: 879-889

    • DOI

      10.1097/nen.0b013e3182303745

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Accumulation of autophagic adaptor protein, p62/sequestosome 1, in the brains of Alzheimer's disease2013

    • Author(s)
      Kunikazu Tanji, Tomoh Matsumiya, Atsushi Maruyama, Saori Odagiri, Fumiaki Mori, Ken Itoh, Akiyoshi Kakita, Hitoshi Takahashi and Koichi Wakabayashi
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] アルツハイマー病とシヌクレイノパチーにおけるストレス防御システム関連タンパク質の検討2013

    • Author(s)
      丹治 邦和, 丸山 敦史, 小田桐 紗織, 森文秋, 伊東 健, 柿田 明美, 高橋 均, 若林 孝一
    • Organizer
      Nuero2013 第36回日本神経科学大会
    • Place of Presentation
      京都市
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経変性疾患脳におけるユビキチンリガーゼ Keap1 の解析2013

    • Author(s)
      丹治 邦和, 丸山 敦史, 小田桐 紗織, 森文秋, 伊東 健, 柿田 明美, 高橋 均, 若林 孝一
    • Organizer
      第54回日本神経病理学会
    • Place of Presentation
      東京
    • Related Report
      2013 Final Research Report
  • [Presentation] Accumulation of autophagic adaptor protein, p62/sequestosome 1, in the brains of Alzheimer’s disease2013

    • Author(s)
      Kunikazu Tanji, Tomoh Matsumiya, Atsushi Maruyama, Saori Odagiri, Fumiaki Mori, Ken Itoh, Akiyoshi Kakita, Hitoshi Takahashi and Koichi Wakabayashi
    • Organizer
      15th International Congress of Immunology,
    • Place of Presentation
      Milan, Italy
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経変性疾患脳におけるユビキチンリガーゼKeap1の解析2013

    • Author(s)
      丹治 邦和, 丸山 敦史, 小田桐 紗織, 森 文秋, 伊東 健, 柿田 明美, 高橋 均, 若林 孝一
    • Organizer
      第54回日本神経病理学会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] アルツハイマー病とシヌクレイノパチーにおけるストレス防御システム関連タンパク質の検討2013

    • Author(s)
      丹治 邦和, 丸山 敦史, 小田桐 紗織, 森 文秋, 伊東 健, 柿田 明美, 高橋 均, 若林 孝一
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] p62/sequestosome 1 binds to TDP-43 in the brains of frontotemporal lobar degeneration with TDP-43 inclusions2012

    • Author(s)
      Kunikazu TANJI1, Haixin ZHANG1, Fumiaki MORI1, Akiyoshi KAKITA2, Hitoshi TAKAHASHI3 and Koichi WAKABAYASHI1
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋市
    • Related Report
      2012 Research-status Report
  • [Presentation] レビー小体病におけるオートファゴソーム関連タンパク質の変化2012

    • Author(s)
      丹治邦和, 森 文秋, 柿田明美, 高橋 均, 若林孝一
    • Organizer
      第53回日本神経病理学会
    • Place of Presentation
      新潟市
    • Related Report
      2012 Research-status Report
  • [Presentation] Autophagosomal proteins in alpha-synucleinopathy2011

    • Author(s)
      Kunikazu Tanji, Fumiaki Mori, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
    • Organizer
      The 2nd Congress of Asian Society of Neuropathology
    • Place of Presentation
      Beijing, CHINA,
    • Related Report
      2011 Research-status Report
  • [Book] Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume22013

    • Author(s)
      Tanji K., F. Mori, and K. Wakabayashi
    • Publisher
      Elsevier Inc. Autophagy
    • Related Report
      2013 Final Research Report
  • [Book] Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging2013

    • Author(s)
      Kunikazu Tanji, Fumiaki Mori, Koichi Wakabayashi
    • Total Pages
      8
    • Publisher
      Elsevier Inc.
    • Related Report
      2013 Annual Research Report
  • [Remarks] 弘前大学大学院 医学研究科 脳神経病理学講座

    • URL

      http://hippo.med.hirosaki-u.ac.jp/web/about_kouza.html

    • Related Report
      2013 Annual Research Report

URL: 

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

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