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A novel approach to ALS pathogenesis by investigating conformational equilibrium of TDP-43

Research Project

Project/Area Number 22659171
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionShiga University of Medical Science

Principal Investigator

URUSHITANI Makoto  滋賀医科大学, 分子神経科学研究センター, 准教授 (60332326)

Co-Investigator(Kenkyū-buntansha) KITAHARA Ryo  立命館大学, 薬学部, 准教授 (70512284)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,190,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords神経分子病態学 / TDP-43 / 筋萎縮性側索硬化症 / 高圧NMR解析 / 変性中間体 / ユビキチン化
Research Abstract

TAR DNA-binding protein 43kDa (TDP-43) is implicated in the pathogenesis of amyotrophic lateral sclerosis, the molecular basis of which underlying ALS pathogenesis is yet to be clarified.We have several residues showing irreversible structural change in TDP-43 proteins. Furthermore, antibodies raised against these residues recognized cytoplasmic TDP-43, typical signatures for ALS.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (45 results)

All 2012 2011 2010 Other

All Journal Article (27 results) (of which Peer Reviewed: 18 results) Presentation (12 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] 変異SOD1タンパク質によるALSの病態機序2012

    • Author(s)
      漆谷 真
    • Journal Title

      脳21「筋萎縮性側索硬化症(ALS)の基礎研究」

      Volume: 15 Pages: 9-15

    • Related Report
      2011 Final Research Report
  • [Journal Article] Protein misdirection inside and outside motor neurons in ALS: a possible clue for therapeutic strategies.2011

    • Author(s)
      Ido A, Fukuyama H, Urushitani M.
    • Journal Title

      Int J Mol Sci

      Volume: 12 Pages: 6980-7003

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] An autopsy case of SOD1-related ALS with TDP-43 positive inclusions.2011

    • Author(s)
      Okamoto Y, Ihara M, Urushitani M, Yamashita H, Kondo T, Tanigaki A, Oono M, Kawamata J, Ikemoto A, Kawamoto A, Takahashi R, Ito H.
    • Journal Title

      Neurology

      Volume: 77 Pages: 1995-1997

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Colocalization of 14-3-3 Proteins with SOD1 in Lewy Body-Like Hyaline Inclusions in Familial Amyotrophic Lateral Sclerosis Cases and the Animal Model.2011

    • Author(s)
      Okamoto Y, Shirakashi Y, Ihara M, Urushitani M, Oono M, Kawamoto Y, Yamashita H, Shimohama S, Kato S, Hirano A, Tomimoto H, Ito H, Takahashi R.
    • Journal Title

      PLoS ONE

      Volume: 6

    • NAID

      120003163709

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo detection of amyloid β deposition using (19)F magnetic resonance imaging with a (19)F-containing curcumin derivative in a mouse model of Alzheimer's disease.2011

    • Author(s)
      Yanagisawa D, Amatsubo T, Morikawa S, Taguchi H, Urushitani M, Shirai N, Hirao K, Shiino A, Inubushi T, Tooyama I.
    • Journal Title

      Neuroscience.

      Volume: 184 Pages: 120-127

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 筋萎縮性側索硬化症の免疫療法2011

    • Author(s)
      漆谷 真
    • Journal Title

      炎症と免疫「神経免疫の新展開」

      Volume: 11月号(19) Pages: 557-563

    • Related Report
      2011 Final Research Report
  • [Journal Article] 神経変性疾患に対する免疫療法の現状2011

    • Author(s)
      大野美樹、漆谷 真
    • Journal Title

      細胞工学「脳内免疫システム」

      Volume: 10月号(30) Pages: 1054-1059

    • Related Report
      2011 Final Research Report
  • [Journal Article] Protein misdirection inside and outside motor neurons in ALS : a possible clue for therapeutic strategies2011

    • Author(s)
      Ido A, et al
    • Journal Title

      Int J Mol Sci

      Volume: 12 Issue: 10 Pages: 6980-7003

    • DOI

      10.3390/ijms12106980

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An autopsy case of SOD1-related ALS with TDP-43 positive inclusions2011

    • Author(s)
      Okamoto Y, Ihara M, Urushitani M, Yamashita H, Kondo T, Tanigaki A, Oono M, Kawamata J, Ikemoto A, Kawamoto Y, Takahashi R, Ito H
    • Journal Title

      Neurology

      Volume: 77:1993-1995 Issue: 22 Pages: 1993-1995

    • DOI

      10.1212/wnl.0b013e31823a0cfc

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Co localization of 14-3-3 proteins with SOD1 in Lewy Body-like hyaline inclusions in familial amyotrophic lateral sclerosis cases and the animal model2011

    • Author(s)
      Okamoto Y, Shirakashi Y, Ihara M, Urushitani M, Oono M, Kawamoto Y, Yamashita H, Shimohama S, Kato S, Hirano A, Tomimoto H, Ito H, Takahashi R
    • Journal Title

      PLoS One

      Volume: 6 Issue: 5 Pages: e20427-e20427

    • DOI

      10.1371/journal.pone.0020427

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo detection of amyloid β deposition using 19F magnetic resonance imaging with a 19F-containing curcurain derivative in a mouse model of Alzheimer's disease2011

    • Author(s)
      柳沢大治郎
    • Journal Title

      Neuroscience

      Volume: 184 Pages: 120-127

    • DOI

      10.1016/j.neuroscience.2011.03.071

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 筋萎縮性側索硬化症の免疫療法2011

    • Author(s)
      漆谷真
    • Journal Title

      炎症と免疫

      Volume: 119 Pages: 557-563

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 神経変性疾患に対する免疫療法の現状2011

    • Author(s)
      大野美樹、漆谷真
    • Journal Title

      細胞工学

      Volume: 30 Pages: 1054-1059

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Induction of protective immunity by vaccination with wild-type apo SOD1 in the mutant SOD1 transgenic mice.2010

    • Author(s)
      Takeuchi S, Fujiwara N, Ido A, Oono M, Takeuchi Y, Tateno M, Suzuki K, Takahashi R, Tooyama I, Taniguchi N, Julien JP, Urushitani M.
    • Journal Title

      J Neuropathol Exp Neurol.

      Volume: 69 Pages: 1044-1056

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Neuronal overexpression of chromogranin A accelerates disease onset in a mouse model of ALS.2010

    • Author(s)
      Ezzi SA, Lariviere R, Urushitani M, Julien JP.
    • Journal Title

      J Neurochem

      Volume: 115 Pages: 1102-1111

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect between proteasome and autophagosome in the clearance of poly-ubiquitinated TDP-43.2010

    • Author(s)
      Urushitani M, Sato T, Bamba H, Hisa Y, Tooyama I.
    • Journal Title

      J Neurosci Res

      Volume: 88 Pages: 784-797

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular mutant SOD1 induces microglial-mediated motoneuron injury.2010

    • Author(s)
      Zhao W, Beers DR, Henkel JS, Zhang W, Urushitani M, Julien JP, Appel SH.
    • Journal Title

      Glia

      Volume: 58 Pages: 231-43

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer's disease.2010

    • Author(s)
      Yanagisawa D, Shirai N, Amatsubo T, Taguchi H, Hirao K, Urushitani M, Morikawa S, Inubushi T, Kato M, Kato F, Morino K, Kimura H, Nakano I, Yoshida C, Okada T, Sano M, Wada Y, Wada KN, Yamamoto A, Tooyama I.
    • Journal Title

      Biomaterials.

      Volume: 31 Pages: 4179-4185

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 免疫療法によるALSの分子標的治療2010

    • Author(s)
      漆谷 真
    • Journal Title

      医学のあゆみ「ALS Update」

      Volume: 235 Pages: 255-260

    • Related Report
      2011 Final Research Report
  • [Journal Article] TDP-43の異所性局在機構2010

    • Author(s)
      漆谷 真
    • Journal Title

      最新医学「神経変性疾患におけるTDP-43」

      Volume: 65 Pages: 1588-1596

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] 家族性ALSマウスモデルの免疫療法2010

    • Author(s)
      漆谷 真
    • Journal Title

      実験医学増刊号「脳神経系の情報伝達と疾患」

      Volume: 28 Pages: 799-807

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Journal Article] Induction of protective immunity by vaccination with wild-type apo SOD1 in the mutant SOD1 transgenic mice2010

    • Author(s)
      Takeuchi S, Fujiwara N, Ido A, Oono M, Takeuchi Y, Tateno M, Suzuki K, Takahashi R, Tooyama I, Taniguchi N, Julien JP, Urushitani M.
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 69 Pages: 1044-1056

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuronal overexpression of chromogranin A accelerates disease onset in a mouse model of ALS2010

    • Author(s)
      Ezzi SA, Lariviere R, Urushitani M, Julien JP
    • Journal Title

      J Neurochem

      Volume: 115 Pages: 1102-1111

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect between proteasome and autophagosome in the clearance of poly-ubiquitinated TDP-432010

    • Author(s)
      Urushitani M, Sato T, Bamba H , Hisa Y, Tooyama I
    • Journal Title

      J Neurosci Res

      Volume: 88 Pages: 784-797

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular mutant SOD1 induces microglial-mediated motoneuron injury2010

    • Author(s)
      Zhao W, Beers DR, Henkel JS, Zhang W, Urushitani M, Julien JP, Appel SH
    • Journal Title

      Glia

      Volume: 58 Pages: 231-243

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between the tautomeric structures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer's disease2010

    • Author(s)
      Yanagisawa D, Shirai N, Amatsubo T, Taguchi H, Hirao K, Urushitani M, Morikawa S, Inubushi T, Kato M, Kato F, Morino K, Kimura H, Nakano I, Yoshida C, Okada T, Sano M, Wada Y, Wada KN, Yamamoto A , Tooyama I
    • Journal Title

      Biomaterial

      Volume: 31 Pages: 4179-418

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 免疫療法によるALSの分子標的治療2010

    • Author(s)
      漆谷 真
    • Journal Title

      医学のあゆみ

      Volume: 235 Pages: 255-260

    • Related Report
      2010 Annual Research Report
  • [Presentation] Variant forms of human chromogranin B fail to interact with mutant SOD1.2011

    • Author(s)
      Ohta Y, Audet JN, Phaneuf D, Urushitani M, Julien JP.
    • Organizer
      Annual Meeting of Neuroscience.
    • Place of Presentation
      ワシントンD.C.(米国)
    • Year and Date
      2011-11-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Variant forms of human chromogranin B fail to interact with mutant SOD12011

    • Author(s)
      太田康之, ら
    • Organizer
      Annual Meeting of Society for Neuroscience 2011
    • Place of Presentation
      ワシントンDC(米国)
    • Year and Date
      2011-11-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] ALSモデルマウスにおけるトランスグルタミナーゼ2の誘導2011

    • Author(s)
      大野 美樹, 井戸 明美, 松本 紋子, 谷口 直之, 高橋 良輔, 漆谷 真
    • Organizer
      第34回日本神経科学大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 筋萎縮性側索硬化症の抗体療法2011

    • Author(s)
      漆谷 真
    • Organizer
      第52回日本神経学会学術集会シンポジウム;神経変性疾患における抗体療法
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-20
    • Related Report
      2011 Final Research Report
  • [Presentation] 神経変性疾患における抗体療法「筋萎縮性側索硬化症の抗体療法」2011

    • Author(s)
      漆谷真
    • Organizer
      第52回日本神経学会学術集会
    • Place of Presentation
      名古屋(招待講演)
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 7th ALS Research Forum, ALS Society of Canada2011

    • Author(s)
      Makoto Urushitani
    • Organizer
      Molecular targeting strategies against misfolded proteins in ALS
    • Place of Presentation
      トロント(カナダ)
    • Year and Date
      2011-05-01
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular targeting strategies against misfolded proteins in ALS2011

    • Author(s)
      漆谷真
    • Organizer
      7th ALS Research Forum, ALS Society of Canada
    • Place of Presentation
      トロント(カナダ)(招待講演)
    • Year and Date
      2011-05-01
    • Related Report
      2011 Annual Research Report
  • [Presentation] ALSの免疫療法2010

    • Author(s)
      漆谷 真
    • Organizer
      Neuro2010 (第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会) シンポジウム 「若手研究者が展開する筋萎縮性側索硬化症研究の将来展望」(兼シンポジウムオーガナイザー)
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-13
    • Related Report
      2011 Final Research Report
  • [Presentation] 筋萎縮性側索硬化症研究におけるモデル動物のインパクト2010

    • Author(s)
      漆谷 真
    • Organizer
      第107回関西実験動物研究会
    • Place of Presentation
      大津市(招待講演)
    • Year and Date
      2010-09-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] ALSの免疫療法2010

    • Author(s)
      漆谷 真
    • Organizer
      euro 2010(第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会 合同大会)シンポジウム;若手研究者が展開する筋萎縮性側索硬化症研究の将来展望
    • Place of Presentation
      神戸市(招待講演)
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] TDP-43の異所性局在とALSの病理現象との関連について2010

    • Author(s)
      漆谷 真、佐藤尚志
    • Organizer
      第51回日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-21
    • Related Report
      2011 Final Research Report
  • [Presentation] TDP-43の異所性局在とALSの病理現象との関連について2010

    • Author(s)
      漆谷 真、佐藤尚志
    • Organizer
      第51回 日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-05-21
    • Related Report
      2010 Annual Research Report
  • [Book] 認知症診療ハンドブック(宇高不可思編)2012

    • Author(s)
      漆谷 真
    • Publisher
      医歯薬ジャーナル(印刷中)
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.shiga-med.ac.jp/~uru/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.shiga-med.ac.jp/~uru/index.html

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] TDP-43の凝集体が蓄積する疾患の発症リスクを予測する方法、診断薬及び治療薬2012

    • Inventor(s)
      漆谷真、藤原範子、伊東秀文
    • Industrial Property Rights Holder
      滋賀医科大学、兵庫医科大学、京都大学
    • Industrial Property Number
      2012-028737
    • Filing Date
      2012-02-13
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] TDP-43の凝集体が蓄積する疾患の発症リスクを予測する方法、診断薬及び治療2012

    • Inventor(s)
      漆谷真、藤原範子、伊東秀文
    • Industrial Property Rights Holder
      滋賀医科大学、兵庫医科大学、京都大学
    • Industrial Property Number
      2012-028737
    • Filing Date
      2012-02-13
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] IMAGING DIAGNOSTIC AGENT AND EXTRACORPOREAL DIAGNOSTIC AGENT FOR INCURABLE NEUROLOGICAL DISEASES2010

    • Inventor(s)
      遠山育夫、漆谷 真、田口弘康、森川茂弘、柳沢大二郎、雨坪知音、白井伸明、平尾浩一、加藤雅也、木村博彦、岡田隆史
    • Industrial Property Rights Holder
      滋賀医科大学、滋賀県、石原産業、JST
    • Filing Date
      2010-02-26
    • Related Report
      2011 Final Research Report
    • Overseas

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Published: 2010-08-23   Modified: 2016-04-21  

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