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

• Project/Area Number: 22659171
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Shiga 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: ¥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.

Research Products

• [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
• [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
  • 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
  • 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
  • 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
  • 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
• [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
• [Journal Article] Protein misdirection inside and outside motor neurons in ALS : a possible clue for therapeutic strategies (2011)
  • Author(s): Ido A, et al
  • Journal Title: Int J Mol Sci Volume: 12 Issue: 10 Pages: 6980-7003
  • DOI: 10.3390/ijms12106980
  • 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 Y, Takahashi R, Ito H
  • Journal Title: Neurology Volume: 77:1993-1995 Issue: 22 Pages: 1993-1995
  • DOI: 10.1212/wnl.0b013e31823a0cfc
  • 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 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 Issue: 5 Pages: e20427-e20427
  • DOI: 10.1371/journal.pone.0020427
  • 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 disease (2011)
  • Author(s): 柳沢大治郎
  • Journal Title: Neuroscience Volume: 184 Pages: 120-127
  • DOI: 10.1016/j.neuroscience.2011.03.071
  • 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
• [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
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
  • 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
  • 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
  • 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: 231-243
  • 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: Biomaterial Volume: 31 Pages: 4179-418
  • 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
• [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
• [Presentation] Variant forms of human chromogranin B fail to interact with mutant SOD1 (2011)
  • 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
• [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
• [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
• [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
• [Presentation] 7th ALS Research Forum, ALS Society of Canada (2011)
  • 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
• [Presentation] Molecular targeting strategies against misfolded proteins in ALS (2011)
  • 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
• [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
• [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
• [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
• [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
• [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
• [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）
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~uru/index.html
• [Remarks]
  • URL: http://www.shiga-med.ac.jp/~uru/index.html
• [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
• [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
• [Patent(Industrial Property Rights)] IMAGING DIAGNOSTIC AGENT AND EXTRACORPOREAL DIAGNOSTIC AGENT FOR INCURABLE NEUROLOGICAL DISEASES (2010)
  • 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
  • Overseas