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In vivo analysis of suppression of the alpha-synuclein expression as a Parkinson's dsiease therapeutic target

Research Project

Project/Area Number 23591230
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionYamagata University

Principal Investigator

ARAWAKA Shigeki  山形大学, 医学部, 講師 (00344789)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords神経内科 / 神経病態学 / パーキンソン病 / 神経毒性 / モデル動物 / 神経内科学 / 神経病態 / 動物モデル
Research Abstract

To investigate whether suppression of the a-synuclein expression level has a potential for Parkinson's disease therapy, this study was aimed at making an animal model that is capable of externally controlling the target gene expression by using a Tet-off system-based adeno-associated viral vector. We constructed three different vectors, which collectively contained Tet-off and target gene expression elements. We assessed the suppressive efficiency of these vectors on the a-synuclein expression in cultured cells. We found that one newly developed vector significantly reduced the expression of a-synuclein by the Tet-off system. We then obtained the viral particles containing this vector. It took a considerable time to select this vector, because there is a little information on this kind of vectors. Unfortunately, we did not reach the experimental step to see the effect of this vector in the animal. However, we could prepare the basic materials to perform in vivo study in the future.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (25 results)

All 2014 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (13 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Zonisamide attenuatesα-synuclein neurotoxicity by an aggregation-independent mechanism in a rat model of familial Parkinson's disease2014

    • Author(s)
      Arawaka S, Fukushima S, Sato H, Sasaki A, Koga K, Koyama S, Kato T
    • Journal Title

      PLoS One

      Volume: 9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Zonisamide attenuates α-synuclein neurotoxicity by an aggregation-independent mechanism in a rat model of familial Parkinson's disease.2014

    • Author(s)
      Arawaka S, Fukushima S, Sato H, Sasaki A, Koga K, Koyama S, Kato T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 2 Pages: e89076-e89076

    • DOI

      10.1371/journal.pone.0089076

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serine 129 phosphorylation of membrane-associated synuclein modulates dopamine transporter function in a G protein-coupled receptor kinase-dependent manner2013

    • Author(s)
      Hara S, Ar awaka S, Sato H, Machiya Y, Cui C, Sasaki A, Koyama S, Kato T
    • Journal Title

      Mol Biol Cell

      Volume: 24 Pages: 1649-1660

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of Ser129-phosphorylation ofα-synuclein in neurodegeneration of Parkinson's disease : a review of in vivo models2013

    • Author(s)
      Sato H, Kato T, Ar awaka S
    • Journal Title

      Rev Neurosci

      Volume: 24 Pages: 115-123

    • Related Report
      2013 Final Research Report
  • [Journal Article] Serine 129 phosphorylation of membrane-associated synuclein modulates dopamine transporter function in a G protein-coupled receptor kinase-dependent manner.2013

    • Author(s)
      Hara S, Arawaka S, Sato H, Machiya Y, Cui C, Sasaki A, Koyama S, Kato T.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 24 Issue: 11 Pages: 1649-1660

    • DOI

      10.1091/mbc.e12-12-0903

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of Ser129 phosphorylation of α-synuclein in neurodegeneration of Parkinson’s disease: a review of in vivo models2013

    • Author(s)
      Sato H, Kato T, Arawaka S
    • Journal Title

      Reviews in the Neuroscience

      Volume: 2 Issue: 2 Pages: 115-124

    • DOI

      10.1515/revneuro-2012-0071

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
  • [Journal Article] Authentically phosphorylated alpha-synuclein at Ser129 accelerates neurodegeneration in a rat model of familial Parkinson's disease2011

    • Author(s)
      Sato H, Ar awaka S, Hara S, Fukushima S, Koga K, Koyama S, Kato, T
    • Journal Title

      J Neurosci

      Volume: 31 Pages: 16884-16894

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Authentically phosphorylated α-synuclein at Ser129 accelerates neurodegeneration in a rat model of familial Parkinson’s disease.2011

    • Author(s)
      Sato, H., Arawaka, S., Hara, S., Fukushima, S., Koga, K., Koyama, S., and Kato, T.
    • Journal Title

      Journal of Neuroscience

      Volume: 31 Pages: 16884-16894

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] ウエスタンブロットにおける固定液を用いたシグナル増強法の検討:α-シヌクレイン微量検出の試み2013

    • Author(s)
      佐々木飛翔,荒若繁樹,加藤丈夫
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜,横浜市
    • Year and Date
      2013-09-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ミトコンドリア障害によるα-シヌクレインSer129リン酸化促進機序の検討2013

    • Author(s)
      荒若繁樹,福島進吾,加藤丈夫
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム,東京都
    • Year and Date
      2013-05-29
    • Related Report
      2013 Final Research Report
  • [Presentation] ウェスタンブロットにおける固定液を用いたシグナル増強法の検討法:α-シヌクレイン微量検出の試み2013

    • Author(s)
      佐々木 飛翔、荒若 繁樹、加藤 丈夫
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] ミトコンドリア障害によるα-シヌクレインSer129リン酸化促進機序の検討2013

    • Author(s)
      荒若 繁樹、福島 進吾、小山 信吾、加藤 丈夫
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム、東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] α-シヌクレインSer129リン酸化反応における細胞内カルシウムの効果:パーキンソン病の病態への関与について2012

    • Author(s)
      佐々木飛翔,荒若繁樹,福島進吾,加藤丈夫
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      マリンメッセ福岡,福岡市
    • Year and Date
      2012-12-15
    • Related Report
      2013 Final Research Report
  • [Presentation] α-シヌクレインによるラットドパミン神経細胞変性に対するゾニサミドの効果2012

    • Author(s)
      荒若繁樹,福島進吾,佐藤裕康,古賀香織,小山信吾,加藤丈夫
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京国際フォーラム,東京都
    • Year and Date
      2012-05-24
    • Related Report
      2013 Final Research Report
  • [Presentation] α-シヌクレインによるラットドパミン神経細胞変性に対するゾニサミドの効果2012

    • Author(s)
      荒若 繁樹、福島 進吾、佐藤 裕康、古賀 香織、小山 信吾、加藤 丈夫
    • Organizer
      第53回日本神経学会
    • Place of Presentation
      東京国際フォーラム、東京
    • Related Report
      2012 Research-status Report
  • [Presentation] α-シヌクレイン発現ラットモデルにおけるゾニサミドの神経保護効果の検討2012

    • Author(s)
      荒若 繁樹、加藤 丈夫
    • Organizer
      第30回日本神経治療学会
    • Place of Presentation
      北九州国際会議場、北九州
    • Related Report
      2012 Research-status Report
  • [Presentation] α-シヌクレインSer129リン酸化反応における細胞内カルシウムの効果:パーキンソン病の病態への関与について2012

    • Author(s)
      佐々木飛翔、荒若 繁樹、福島 進吾、加藤 丈夫
    • Organizer
      第85回日本生化学学会
    • Place of Presentation
      福岡国際会議場、福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Authentically phosphorylatedα-synuclein at Ser129 accelerates neurodegeneration in a rat model of familial Parkinson's disease2011

    • Author(s)
      Sato H, Arawaka S, Hara S, Fukushima S, Koyama S, Kato T .
    • Organizer
      Neuroscience meeting 2011
    • Place of Presentation
      Walter E. Washington Convention Center, Washington, DC., USA
    • Year and Date
      2011-11-14
    • Related Report
      2013 Final Research Report
  • [Presentation] ドパミン取り込みにおけるα-シヌクレインSer129リン酸化の効果2011

    • Author(s)
      佐々木飛翔,荒若繁樹,原進,佐藤裕康,福島進吾,加藤丈夫
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館,京都市
    • Year and Date
      2011-09-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Ser129リン酸化α-シヌクレインのドパミン取り込みに対する効果2011

    • Author(s)
      荒若繁樹,原進,佐藤裕康,福島進吾,小山信吾,加藤丈夫
    • 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,名古屋市
    • Year and Date
      2011-05-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Authentically phosphorylated α-synuclein at Ser129 accelerates neurodegeneration in a rat model of familial Parkinson’s disease.2011

    • Author(s)
      Sato, H., Arawaka, S., Hara, S., Fukushima, S., Koyama, S., and Kato, T.
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      アメリカ合衆国(ワシントンDC)
    • Related Report
      2011 Research-status Report
  • [Book] 遺伝子・再生医療研究から学ぶパーキンソン病.α-Synuclein(PARK1/4)機能における翻訳後修飾の役割-リン酸化研究の現状.医学のあゆみ2472013

    • Author(s)
      荒若繁樹、加藤丈夫
    • Related Report
      2013 Final Research Report
  • [Book] 医学のあゆみ. 遺伝子・再生医療研究から学ぶパーキンソン病.2013

    • Author(s)
      荒若 繁樹、加藤 丈夫
    • Total Pages
      100
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2013 Annual Research Report
  • [Remarks] 山形大学医学部内科学第3講座

    • URL

      http://minfo.id.yamagata-u.ac.jp/naika3/index.html

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://minfo.id.yamagata-u.ac.jp/naika3/index.html

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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