Establishment of novel Drosophila models of ALS expressing TDP-43, and analyses of its pathomechanisms

• Project/Area Number: 22790839
• 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: FUJIKAKE Nobuhiro 独立行政法人国立精神・神経医療研究センター, 疾病研究第四部, 科研費研究員 (60467595)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 遺伝子 / 遺伝学 / 神経科学 / 筋萎縮性側索硬化症 / ALS / TDP-43 / 神経変性疾患 / ショウジョウバエ

Research Abstract

Amyotrophic lateral sclerosis(ALS) is a progressive neurodegenerative disease which is characterized by selective motor neuron degeneration in the brain and spinal cord. Recent studies demonstrate that abnormalities of TDP-43 are involved in the pathomechanism of neurodegeneration in ALS. To elucidate the pathomechanism of TDP-43-induced neurodegeneration in vivo, we employed Drosophila melanogaster to model ALS because of its advantage in suitability for genetic-screening. We identified autophagy-related genes such as Atg6 and Atg12 as modifiers of neurodegeneration in ALS model flies expressing TDP-43. Our results suggest that the autophagy-mediated protein degradation pathway is involved in TDP-43-induced neurodegeneration in ALS.

Research Products

• [Journal Article] ショウジョウバエなど小動物を用いた筋萎縮性側索硬化症モデル (2012)
  • Author(s): 藤掛伸宏、長野清一、永井義隆
  • Journal Title: 神経内科 Volume: vol.76 Pages: 266-274
  • URL: http://www.kahyo.com/item/S201203-763
• [Journal Article] ショウジョウバエなど小動物を用いた筋萎縮性側索硬化症モデル (2012)
  • Author(s): 藤掛伸宏, 長野清一, 永井義隆
  • Journal Title: 神経肉科 Volume: 76 Pages: 266-274
• [Journal Article] ショウジョウバエモデルから解明されたTDP-43プロテイノパチーの分子病態 (2011)
  • Author(s): 永井義隆、藤掛伸宏
  • Journal Title: Dementia Japan Volume: vol.25 Pages: 129-136
  • URL: http://www.sasappa.co.jp/online/abstract/jsdr/1/25/html/101250206.html
• [Journal Article] α-Synuclein transgenic Drosophila as a model of Parkinson's Disease and related synucleinopathies (2011)
  • Author(s): Mizuno H, Fujikake N, Wada K, Nagai Y
  • Journal Title: Parkinsons Dis Volume: 2011 Pages: 212706-212706
  • DOI: 10.4061/2011/212706
  • Peer Reviewed
• [Journal Article] DP-43プロテイノパチーの動物モデル (2011)
  • Author(s): 永井義隆、藤掛伸宏
  • Journal Title: 最新医学 Volume: vol.65 Pages: 1603-1613
  • URL: http://www.saishin-igaku.co.jp/backnum/2010/y6507.html
• [Journal Article] ショウジョウバエモデルから解明されたTDP-43プロテイノパチーの分子病態 (2011)
  • Author(s): 永井義隆, 藤掛伸宏
  • Journal Title: Dementia Japan Volume: 25 Pages: 129-136
• [Journal Article] α-Synuclein Transgenic Drosophila As a Model of Parkinson's Disease and Related Synucleinopathies. (2011)
  • Author(s): Mizuno H., et al.
  • Journal Title: Parkinson's Disease Volume: 2011 Pages: 212706-212706
  • Peer Reviewed
• [Journal Article] TDP-43プロテイノパチーの動物モデル (2011)
  • Author(s): 永井義隆, 他
  • Journal Title: 最新医学 Volume: 65 Pages: 1603-1613
• [Journal Article] Genetic Testing for Huntington's Disease in Parkinsonism (2010)
  • Author(s): Rahman MS, Nagai Y, Popiel HA, Fujikake N, et al
  • Journal Title: Mymensingh Medical Journal Volume: vol.19 Pages: 510-514
  • URL: http://www.banglajol.info/index.php/MMJ/article/view/6708
  • Peer Reviewed
• [Journal Article] Genetic Testing for Huntington's Disease in Parkinsonism. (2010)
  • Author(s): Rahman M.S., et al.
  • Journal Title: Mymensingh Medical Journal Volume: 19 Pages: 510-514
  • Peer Reviewed
• [Presentation] 高栄養負荷は神経変性疾患モデルショウジョウバエにおける神経変性を増悪する (2011)
  • Author(s): 鈴木マリ、藤掛伸宏、和田圭司、永井義隆
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] TDP-43を発現するALSモデルショウジョウバエにおけるオートファジー系蛋白質分解の関与 (2011)
  • Author(s): 藤掛伸宏、斉藤勇二、横関明男、小野寺理、和田圭司、永井義隆
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋国際会議場(愛知県)
• [Presentation] Expression of TDP-43 causes neurological phenotypes with an enhancement by FALS mutations in novel Drosophila models of ALS (2011)
  • Author(s): Fujikake N, Saitoh Y, Yokoseki A, Onodera O, Wada K, Nagai Y
  • Organizer: 10th International Conference on Alzheimer's & Parkinson's Diseases
  • Place of Presentation: CCIB Convention Center(Barcelona, Spain)
• [Presentation] Expression of TDP-43 causes neurological phenotypes with an enhancement by FALS mutations in novel Drosophila models of ALS (2011)
  • Author(s): Fujikake N., et al.
  • Organizer: 10th International Conference on Alzheimer's & Parkinson's Diseases
  • Place of Presentation: CCIB Convention Center (Barcelona, Spain)
• [Presentation] TDP-43を発現する新規ALSモデルショウジョウバエの樹立とその病態解析 (2010)
  • Author(s): 藤掛伸宏, 他
  • Organizer: 第33回 日本神経科学会・第53回 日本神経化学会 合同大会
  • Place of Presentation: 神戸コンベンションセンター(兵庫県)
  • Year and Date: 2010-09-03
• [Presentation] Abnormal accumulation of TDP-43 proteins causes neurodegeneration in novel Drosophila models of ALS (2010)
  • Author(s): Fujikake N, Saitoh Y, Yokoseki A, Onodera O, Wada K, Nagai Y
  • Organizer: 3rd International Symposium on Protein Community
  • Place of Presentation: Hotel Nikko(Nara, Japan)
• [Presentation] TDP-43を発現する新規ALSモデルショウジョウバエの樹立とその病態解析 (2010)
  • Author(s): 永井義隆、藤掛伸宏、斉藤勇二、横関明男、小野寺理
  • Organizer: 第33回日本神経科学会・第53回日本神経化学会合同大会
  • Place of Presentation: 神戸コンベンションセンター(兵庫県)
• [Presentation] TDP-43を発現する新規ALSモデルショウジョウバエを用いた病態解析 (2010)
  • Author(s): 永井義隆、藤掛伸宏、斉藤勇二、横関明男、小野寺理、和田圭司
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム(東京都)
• [Presentation] Abnormal accumulation of TDP-43 proteins causes neurodegeneration in novel Drosophila models of ALS. (2010)
  • Author(s): Fujikake N., et al.
  • Organizer: 3rd International Symposium on Protein Community
  • Place of Presentation: Hotel Nikko (Nara, Japan)
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r4/index.html
• [Remarks]
  • URL: http://www.ncnp.go.jp/nin/guide/r4/index.html