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Adenovirus-mediated inhibition of proteolytic and cell death pathways in adult rat motoneurons.

Research Project

Project/Area Number 21500341
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research Institution財団法人東京都医学総合研究所 (2011)
Tokyo Metropolitan Organization for Medical Research (2009-2010)

Principal Investigator

WATABE Kazuhiko  財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 副参事研究員 (30240477)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords運動ニューロン / TDP-43 / FUS / 筋萎縮性側索硬化症 / アデノウイルス / プロテアソーム / オートファジー / ESCRT / shRNA / 顔面神経 / 運動神経損傷
Research Abstract

Impairment of proteolytic machineries has been recognized to participate in motoneuron degeneration in ALS. Furthermore, recent identifications of disease-associated genes that include TDP-43 and FUS have led to open a new era in ALS research. We produced recombinant adenovirus encoding wild type and mutant TDP-43 or FUS, and those encoding shRNAs for proteosome(PSMC1), endosome/ESCRT(VPS24) and autophagy(ATG5) systems to investigate whether the coupled gene transductions in motoneurons elicit ALS pathology. Co-infections of adenovirus encoding shRNA for PSMC1 or ATG5 with TDP-43 or FUS adenovirus enhanced cytoplasmic aggregate formation in motoneurons, suggesting that impairment of proteasome, endosome/ESCRT, or autophagy system accelerates TDP-43 and FUS pathology in ALS.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (48 results)

All 2012 2011 2010 2009 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (27 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Myelination in coculture of established neuronal and Schwann cell lines2012

    • Author(s)
      Sango K, Kawakami E, Yanagisawa H, Takaku S, Tsukamoto M, Utsunomiya K, Watabe K
    • Journal Title

      Histochem Cell Biol

      Volume: 137 Issue: 6 Pages: 829-839

    • DOI

      10.1007/s00418-012-0934-3

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immortalized adult rodent Schwann cells as in vitro models to study diabetic neuropathy2011

    • Author(s)
      Sango K, Yanagisawa H, Takaku S, Kawakami E, Watabe K
    • Journal Title

      Exp Diabetes Res

      Volume: 374943 Pages: 374943-374943

    • DOI

      10.1155/2011/374943

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A morphometric study of the vagus nerve in amyotrophic lateral sclerosis with circulatory collapse2011

    • Author(s)
      Shimizu T, Hayashi M, Kawata A, Mizutani T, Watabe K, Matsubara S
    • Journal Title

      Amyotroph Lateral Scler

      Volume: 12 Issue: 5 Pages: 356-362

    • DOI

      10.3109/17482968.2011.566342

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Metallothionein-III prevents neuronal death and prolongs life span in amyotrophic lateral sclerosis model mice2011

    • Author(s)
      Hashimoto K, Hayashi Y, Watabe K, Inuzuka T, Hozumi I
    • Journal Title

      Neuroscience

      Volume: 189 Pages: 293-298

    • DOI

      10.1016/j.neuroscience.2011.05.034

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneously immortalized adult rat Schwann cells IFRS1 as a vulnerable tool for exploring neuron-Schwann cell interactions2011

    • Author(s)
      Sango K, Kawakami E, Yanagisawa H, Takaku S, Ajiki K, Endo K, Watabe K
    • Journal Title

      J Neurosci Res

      Volume: 89 Issue: 6 Pages: 898-908

    • DOI

      10.1002/jnr.22605

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hyperosmolar hyperglycemic state in advanced amyotrophic lateral sclerosis2011

    • Author(s)
      Shimizu T, Honda M, Ohashi T, Tsujino M, Nagaoka U, Kawata A, Watabe K, Matsubara S, Hayashi H
    • Journal Title

      Amyotroph Lateral Scler

      Volume: 12 Issue: 5 Pages: 309-311

    • DOI

      10.3109/17482968.2010.539234

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Morphological changes of Golgi apparatus in rats after facial nerve injuries2011

    • Author(s)
      Fujita Y, Watabe K, Ikeda K, Mizuno Y, Okamoto K
    • Journal Title

      Neuropathology

      Volume: 31 Issue: 1 Pages: 42-47

    • DOI

      10.1111/j.1440-1789.2010.01123.x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Morphological changes of Golgi apparatus in rats after facial nerve injuries.2011

    • Author(s)
      Fujita Y, et al.
    • Journal Title

      Neuropathology

      Volume: 31 Pages: 42-47

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Presenilin-1 holoprotein is an interacting partner of sarco ER calcium-ATPase and confers resistance against ER stress2010

    • Author(s)
      Jin H, Sanjo N, Uchihara T, Watabe K, St. George-Hyslop P, Fraser PE, Mizusawa H
    • Journal Title

      J Alzheimer Dis

      Volume: 20 Issue: 1 Pages: 261-273

    • DOI

      10.3233/jad-2010-1360

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of an improved mouse model for infantile neuroaxonal dystrophy that shows early disease onset and bears a point mutation in Pla2g62009

    • Author(s)
      Wada H, Yasuda T, Miura I, Watabe K, Sawa C, Kamijuku H, Kojo S, Taniguchi M, Nishino I, Wakana S, Yoshida H, Seino K
    • Journal Title

      Am J Pathol

      Volume: 175 Issue: 6 Pages: 2257-2263

    • DOI

      10.2353/ajpath.2009.090343

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Schwann cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration2009

    • Author(s)
      Wang W, Itoh S, Konno K, Kikkawa T, Ichinose S, Sakai K, Ohkuma T, Watabe K
    • Journal Title

      J Biomed Mater Res A

      Volume: 91 Issue: 4 Pages: 994-1005

    • DOI

      10.1002/jbm.a.32329

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Schwann cell alignment along the oriented electrospun chitosan nanofibers on nerve regeneration2009

    • Author(s)
      Wang W, et al.
    • Journal Title

      J Biomed Mater Res A 91

      Pages: 994-2002

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of an improved mouse model for infantile neuroaxonal dystrophy that shows early disease onset and bears a point mutation in Pla2g62009

    • Author(s)
      Wada H, et al.
    • Journal Title

      Am J Pathol 175

      Pages: 2257-2263

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperosmolar hyperglycemic state in advanced amyotrophic lateral sclerosis.

    • Author(s)
      Shimizu T, et al.
    • Journal Title

      Amyotroph Lateral Scler

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneously immortalized adult rat Schwann cells IFRS1 as a vulnerable tool for exploring neuron-Schwann cell interactions.

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

      J Neurosci Res

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Presenilin-1 holoprotein is an interacting partner of sarco ER calcium-ATPase and confers resistance against ER stress

    • Author(s)
      Jin H, et al.
    • Journal Title

      J Alzheimer Dis (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 高グルコース負荷に伴うシュワン細胞株IFRS1の代謝変化2011

    • Author(s)
      三五一憲,柳澤比呂子,渡部和彦
    • Organizer
      第26回日本糖尿病合併症学会
    • Place of Presentation
      大宮
    • Year and Date
      2011-10-15
    • Related Report
      2011 Final Research Report
  • [Presentation] Myelination in cocultures of established neuronal and Schwann cell lines2011

    • Author(s)
      Sango K, Kawakami E, Yanagisawa H, Takaku S, Watabe K
    • Organizer
      Neuroscience 2011(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 Final Research Report
  • [Presentation] 株化ニューロン・シュワン細胞による共培養系確立・髄鞘形成誘導2011

    • Author(s)
      三五一憲,柳澤比呂子,河上江美子,渡部和彦
    • Organizer
      第22回日本末梢神経学会学術集会
    • Place of Presentation
      宜野湾
    • Year and Date
      2011-09-03
    • Related Report
      2011 Final Research Report
  • [Presentation] Myelination in cocultures of PC12 cells and immortalized IFRS1 Schwann cells2011

    • Author(s)
      Sango K, Yanagisawa H, Kawakami E, Watabe K
    • Organizer
      2011 Peripheral Nerve Society
    • Place of Presentation
      Potomac, MD, USA.
    • Year and Date
      2011-06-27
    • Related Report
      2011 Final Research Report
  • [Presentation] 組換えアデノウイルスを用いたラット運動ニューロンにおけるTDP-43, FUSの細胞体蓄積とプロテアソーム,オートファジー阻害2011

    • Author(s)
      渡部和彦,秋山けい子,河上江美子,高久静香
    • Organizer
      第51回日本神経病理学会総会学術研究会
    • Place of Presentation
      京都
    • Year and Date
      2011-06-04
    • Related Report
      2011 Final Research Report
  • [Presentation] 組換えアデノウイルスを用いたラット運動ニューロンにおけるTDP-43,FUSの細胞体蓄積とプロテアソーム,オートファジー阻害2011

    • Author(s)
      渡部和彦, ら
    • Organizer
      第51回日本神経病理学会総会学術研究会
    • Place of Presentation
      京都
    • Year and Date
      2011-06-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 末梢神経障害研究モデルとしての,ニューロン・シュワン細胞株共培養系の確立2011

    • Author(s)
      三五一憲,柳澤比呂子,河上江美子,渡部和彦
    • Organizer
      第52回日本神経学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-18
    • Related Report
      2011 Final Research Report
  • [Presentation] 成体ラット運動ニューロンへのTDP-43, FUSの遺伝子導入2011

    • Author(s)
      渡部和彦,秋山けい子,河上江美子,高久静香
    • Organizer
      第52回日本神経学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Spontaneously immortalized adult Fischer rat Schwann cells IFRS1 as a valuable tool for exploring neuron-Schwann cell interactions2010

    • Author(s)
      Sango K, Yanagisawa H, Takaku S, Kawakami E, Watabe K
    • Organizer
      第83回日本生化学会大会(BMB2010)
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-08
    • Related Report
      2011 Final Research Report
  • [Presentation] Establishment of spontaneously immortalized adult Fischer rat Schwann cells IFRS12010

    • Author(s)
      Sango K, Ajiki K, Kawakami E, Yanagisawa H, Takaku S, Watabe K
    • Organizer
      Neuroscience 2010
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2010-11-16
    • Related Report
      2011 Final Research Report
  • [Presentation] 成熟ラットシュワン細胞株IFRS1を用いた,糖尿病性神経障害の解析2010

    • Author(s)
      三五一憲,柳澤比呂子,渡部和彦
    • Organizer
      第25回日本糖尿病合併症学会
    • Place of Presentation
      大津
    • Year and Date
      2010-10-22
    • Related Report
      2011 Final Research Report
  • [Presentation] Adenoviral expression of TDP-43 and FUS genes in adult rat motoneurons in vivo2010

    • Author(s)
      Watabe K, Akiyama K, Takaku S, Kawakami E
    • Organizer
      17th International Congress of Neuropathology
    • Place of Presentation
      Salzburg, Austria
    • Year and Date
      2010-09-12
    • Related Report
      2011 Final Research Report
  • [Presentation] Adenoviral expression of TDP-43 and FUS genes in adult rat motoneurons in vivo.2010

    • Author(s)
      Watabe K, et al.
    • Organizer
      17th International Congress of Neuropathology
    • Place of Presentation
      Salzburg, Austria
    • Year and Date
      2010-09-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 成熟ラット由来不死化シュワン細胞株とDRGニューロンとの共培養系の確立2010

    • Author(s)
      三五一憲,渡部和彦
    • Organizer
      第21回日本末梢神経学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-04
    • Related Report
      2011 Final Research Report
  • [Presentation] 不死化シュワン細胞株IFRS1を用いた、ニューロン-シュワン細胞間相互作用の解析2010

    • Author(s)
      三五一憲,安食京子,河上江美子,柳澤比呂子,高久静香,渡部和彦
    • Organizer
      Neuro2010(第53回日本神経化学会大会・第33回日本神経科学大会)
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-03
    • Related Report
      2011 Final Research Report
  • [Presentation] 成体ラット運動ニューロンへのTDP-43, FUSの遺伝子導入2010

    • Author(s)
      渡部和彦,秋山けい子,高久静香,河上江美子
    • Organizer
      Neuro2010(第53回日本神経化学会大会・第33回日本神経科学大会)
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-02
    • Related Report
      2011 Final Research Report
  • [Presentation] Schwann細胞から見たNeuro-Gliology2010

    • Author(s)
      渡部和彦
    • Organizer
      第40回新潟神経学夏期セミナー
    • Place of Presentation
      新潟
    • Year and Date
      2010-08-06
    • Related Report
      2011 Final Research Report
  • [Presentation] Establishment of immortalized adult rodent Schwann cell lines to study peripheral nerve disorders2010

    • Author(s)
      Watabe K, Sango K
    • Organizer
      The First International Conference of Neural Cell Culture
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2010-06-25
    • Related Report
      2011 Final Research Report
  • [Presentation] 新たな糖尿病性神経障害研究モデルとしての,ニューロン-シュワン細胞株共培養系の確立2010

    • Author(s)
      三五一憲,柳澤比呂子,渡部和彦
    • Organizer
      第53回日本糖尿病学会年次学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2010-05-29
    • Related Report
      2011 Final Research Report
  • [Presentation] 成体ラット運動ニューロンへの変異TDP-43, FUSの遺伝子導入2010

    • Author(s)
      渡部和彦,秋山けい子,長竿淳
    • Organizer
      第51回日本神経病理学会総会学術研究会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-23
    • Related Report
      2011 Final Research Report
  • [Presentation] 成熟ラット末梢神経の初代培養系から樹立したシュワン細胞株IFRS1の解析2010

    • Author(s)
      三五一憲,渡部和彦
    • Organizer
      日本病態生理学会
    • Place of Presentation
      奈良
    • Year and Date
      2010-01-23
    • Related Report
      2011 Final Research Report
  • [Presentation] Schwann細胞を用いた糖尿病性神経障害の病態解析2009

    • Author(s)
      三五一憲,渡部和彦
    • Organizer
      第24回日本糖尿病合併症学会
    • Place of Presentation
      岡山
    • Year and Date
      2009-10-09
    • Related Report
      2011 Final Research Report
  • [Presentation] 成熟ラットシュワン細胞株IFRS1の樹立とその解析2009

    • Author(s)
      三五一憲,渡部和彦
    • Organizer
      日本末梢神経学会
    • Place of Presentation
      大宮
    • Year and Date
      2009-09-04
    • Related Report
      2011 Final Research Report
  • [Presentation] ENU mutagenesisによるヒト乳児型軸索ジストロフィーモデルマウスの樹立2009

    • Author(s)
      渡部和彦,和田はるか,澤智華,安田琢和,吉田尚弘,清野研一郎
    • Organizer
      第41回日本臨床分子形態学会総会・学術集会シンポジウム6「軸索ジストロフィーとユビキチン関連蛋白」
    • Place of Presentation
      神戸
    • Year and Date
      2009-09-04
    • Related Report
      2011 Final Research Report
  • [Presentation] 組換えアデノウイルスを用いた成体ラット運動ニューロン損傷における蛋白分解系と細胞死の解析2009

    • Author(s)
      長竿淳,秋山けい子,渡部和彦
    • Organizer
      第50回日本神経病理学会総会学術研究会
    • Place of Presentation
      高松
    • Year and Date
      2009-06-05
    • Related Report
      2011 Final Research Report
  • [Presentation] 組換えアデノウイルスを用いた成体ラット運動ニューロン損傷における蛋白分解系と細胞死の解析2009

    • Author(s)
      長竿淳
    • Organizer
      第50回日本神経病理学会総会学術研究会
    • Place of Presentation
      サンポート高松(高松)
    • Year and Date
      2009-06-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Establishment of a mouse bearing a point mutation in PLA2G6 which show early onset of neuroaxonal dystrophy2009

    • Author(s)
      Wada H, Yasuda T, Sawa C, Kamijuku H, Watabe K, Yoshida H, Seino K
    • Organizer
      4th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2009-05-26
    • Related Report
      2011 Final Research Report
  • [Book] Galectin-1 as a multifunctional molecule in the peripheral nervous system after injury. Basic Principles of Peripheral Nerve Disorders(Ed : Rayegani, S. M.)2012

    • Author(s)
      Sango K, Yanagisawa H, Watabe K, Horie H, Kadoya T
    • Publisher
      InTech
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://tmin.ac.jp

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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