Toxicity of ALS-linked mutant SOD1 mediated by aberrant protein interactions

• Project/Area Number: 22790838
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: KABUTA Tomohiro 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第四部, 室長 (70535765)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 神経分子病態学 / ALS / SOD1 / TDP-43

Research Abstract

We have developed mutant SOD1-transgenic flies that display apparent motor dysfunction. We found that mutant SOD1 interacts with TDP-43. We have demonstrated that most of the mutant SOD1-interacting proteins interacts with 1-23 as of SOD1. We have identified several small compounds that inhibit the aberrant interactions between mutant SOD1 and other cellular proteins.

Research Products

• [Journal Article] Parkinson's disease-associated mutations in alpha-synuelein and UCH-L1 inhibit the unconventional secretion of UCH-L1 (2011)
  • Author(s): Konya C, Hatanaka Y, Fujiwara Y, Uchida K, Nagai Y, Wada K, Kabuta T
  • Journal Title: Neurochem Int Volume: 59 Pages: 251-258
  • URL: http://www.sciencedirect.com/science/article/pii/S0197018611001860
  • Peer Reviewed
• [Journal Article] Localization of MAP1? LC3 in vulnerable neurons and Lewy bodies in brains of patients with dementia with Lewy bodies (2011)
  • Author(s): Higashi S, Moore DJ, Minegishi M, Kasanuki K, Fujishiro H, Kabuta T, Togo T, Katsuse 0, Uchikado H, Furukawa Y, Hino H, Kosaka K, Sato K, Arai H, Wada K, Iseki E
  • Journal Title: J Neuropathol Exp Neurol Volume: 70 Pages: 264-280
  • URL: http://ovidsp.tx.ovid.com/sp-3.5.1a/ovidweb.cgi?QS2=434f4e1a73d37e8c54b7bccef7797d0edb53f05ad3a4d1c3b26bd796923b86f733e687cf678e4da62d9832a1f418fb666flObb3957c0173d25b9268c1a52clee3d82114fc19965926abca3e829ea7c690748e18d561c00469a9f385a8b938a7a1f44aea94be
  • Peer Reviewed
• [Journal Article] Parkinson's disease-associated mutations in alpha-synuclein and UCH-L1 inhibit the unconventional secretion of UCH-L1 (2011)
  • Author(s): Konya, C.
  • Journal Title: Neurochem Int Volume: 59 Issue: 2 Pages: 251-258
  • DOI: 10.1016/j.neuint.2011.05.012
  • Peer Reviewed
• [Journal Article] Localization of MAP1-LC3 in vulnerable neurons and Lewy bodies in brains of patients with dementia with Lewy bodies. (2011)
  • Author(s): Higashi S, Moore DJ, Minegishi M, Kasanuki K, Fujishiro H, Kabuta T, Togo T, Katsuse O, Uchikado H, Furukawa Y, Hino H, Kosaka K, Sato K, Arai H, Wada K, Iseki E
  • Journal Title: J Neuropathol Exp Neurol Volume: 70(4) Issue: 4 Pages: 264-80
  • DOI: 10.1097/nen.0b013e318211c86a
  • Peer Reviewed
• [Journal Article] TDP-43 Physically Interacts with Amyotrophic Lateral Sclerosis? Linked Mutant CuZn Superoxide Dismutase (2010)
  • Author(s): Higashi S, Tsuchiya Y, Araki T, Wada K, Kabuta T
  • Journal Title: Neurochem. Int Volume: 57 Pages: 906-913
  • URL: http://www.sciencedirect.com/science/article/pii/S0197018610003001
  • Peer Reviewed
• [Journal Article] IGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1? induced ERK1/2 activation (2010)
  • Author(s): Higashi S, Iseki E, Minegishi M, Togo T, Kabuta T, Wada K
  • Journal Title: Neurochem Volume: 115 Pages: 423-437
  • URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2010.06930.x/abstract;jsessionid=4CF7294F753B1E0F660FE9A227C207FF.d03t035
  • Peer Reviewed
• [Journal Article] Reduction of abnormal behavioral response to brief restraint by information from other mice in dystrophin? deficient mdx mice (2010)
  • Author(s): Yamamoto K, Yamada D, Kabuta T, Takahashi A, Wada K, Sekiguchi M
  • Journal Title: Neuromuscul. Disord Volume: 20 Pages: 505-511
  • URL: http://www.sciencedirect.com/science/article/pii/S0960896610002191
  • Peer Reviewed
• [Journal Article] Deficiency of ubiquitin carboxy-terminal hydrolase-L1(UCH-L1) leads to vulnerability to lipid peroxidation (2010)
  • Author(s): Nagamine S, Kabuta T, Furuta A, Yamamoto K, Takahashi A, Wada K
  • Journal Title: Neurochem. Int Volume: 57 Pages: 102-110
  • URL: http://www.sciencedireet.com/seience/article/pii/S019701861000149X
  • Peer Reviewed
• [Journal Article] Insulin receptor substrate-3, interacting with Bel-3, enhances p50 NF? kappaB activity (2010)
  • Author(s): Kabuta T, Hakuno F, Cho Y, Yamanaka D, Chida K, Asano T, Wada K, Takahashi S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 394 Pages: 697-702
  • URL: http://www.sciencedireet.com/seience/article/pii/S0006291X10004924
  • Peer Reviewed
• [Journal Article] Identification of a novel chemical potentiator and inhibitors of UCH? L1 by in silico drug screening (2010)
  • Author(s): Mitsui T, Hirayama K, Aoki S, Nishikawa K, Uchida K, Matsumoto T, Kabuta T, Wada K
  • Journal Title: Neurochem. Int Volume: 56 Pages: 679-686
  • URL: http://www.sciencedireet.com/seience/article/pii/S0197018610000549
  • Peer Reviewed
• [Journal Article] TDP-43 physically interacts with amyotrophic lateral sclerosis-linked mutant CuZn superoxide dismutase. (2010)
  • Author(s): Higashi S., et al.
  • Journal Title: Neurochemistry International Volume: 57 Pages: 906-913
  • Peer Reviewed
• [Journal Article] GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1-induced ERK1/2 activation. (2010)
  • Author(s): Higashi S., et al.
  • Journal Title: Journal of Neurochemistry Volume: 115 Pages: 423-437
  • Peer Reviewed
• [Journal Article] Deficiency of ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) leads to vulnerability to lipid peroxidation. (2010)
  • Author(s): Nagamine S, et al.
  • Journal Title: Neurochemistry International Volume: 57 Pages: 102-110
  • Peer Reviewed
• [Presentation] パーキンソン病関連変異型UCH-L1の異常な分子性質 (2011)
  • Author(s): 株田智弘
  • Organizer: 第54回日本神経化学会大会シンポジウム
  • Place of Presentation: 加賀
  • Year and Date: 2011-09-26
• [Presentation] パーキンソン病関連変異型UCH-L1の異常な分子性質 (2011)
  • Author(s): 株田智弘
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 瑠璃光(加賀)(シンポジウム)(招待講演)
  • Year and Date: 2011-09-26
• [Presentation] 筋萎縮性側索硬化症モデルショウジョウバエにおける単量体mutant SOD1の神経毒性 (2011)
  • Author(s): 麸田智弘
  • Organizer: 第34回日本神経科学大会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-16
• [Presentation] 筋萎縮性側索硬化症モデルショウジョウバエにおける単量体mutant SOD1の神経毒性 (2011)
  • Author(s): 株田智弘
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(横浜)(シンポジウム)(招待講演)
  • Year and Date: 2011-09-16
• [Presentation] UCH-L1によるシナプス調節機構の解析 (2011)
  • Author(s): 畑中悠佑,紺谷千穂,藤原悠紀,向野佳奈子,浅羽研亮,和田圭司,麸田智弘
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] 家族性パーキンソン病変異によるUCH-L1の分泌減少 (2010)
  • Author(s): 紺谷千穂、藤原悠紀、永井義隆、内田健康、和田圭司、株田智弘
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 家族性パーキンソン病変異によるUCH-L1の分泌減少 (2010)
  • Author(s): 紺谷千穂, ら
  • Organizer: BMB2010
  • Place of Presentation: 神戸、神戸コンベンションセンター
  • Year and Date: 2010-12-07
• [Presentation] GIGYF2 is present in endosomal compartments in the mammalian brains and enhances IGF-1? induced ERK1/2 activation (2010)
  • Author(s): Higashi S, Iseki E, Minegishi M, Togo T, Kabuta T, Wada K
  • Organizer: 14th European Federation of Neurological Societies(EFNS) Congress
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 2010-09-26
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r4/index.html