• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Dopamin neuron specific modification of alpha-synulein and novel therapeutic target against Parkinson's disease

Research Project

Project/Area Number 24591262
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKASO Kazuhiro  鳥取大学, 医学部, 准教授 (30379648)

Co-Investigator(Renkei-kenkyūsha) MATSURA Tatusya  鳥取大学, 医学部, 教授 (00199746)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsパーキンソン病 / α-synuclein / ドパミン / カテコールアミン / メチオニン / α-シヌクレイン / 酸化修飾 / 翻訳後修飾 / ドーパミン
Outline of Final Research Achievements

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopamine (DA) neurons. However, it is not well understood why PD-related pathogenesis occurs in DA neurons. We investigated the interaction between DA and a-synuclein (asyn) with regard to cytotoxicity. We generated PC12 cells expressing human asyn, as well as several asyn mutants using a Tet-OFF system. Overexpression of wildtype asyn decreased cell viability in long-term cultures, while an inhibitor of tyrosine hydroxylase blocked this vulnerability, suggesting that asyn-related cytotoxicity is associated with DA metabolism. The vulnerabilities of all mutant cell lines were lower than that of wildtype asyn-expressing cells. Moreover, asyn containing DA-mediated oxidized methionine (Met(O)) was detected in our cell lines. Met(O) was lower in methionine mutant cells, especially in the M127A mutant cells. Moreover, Y125 and S129 may act as enhancers of this DA-related modification of asyn.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (12 results)

All 2015 2014 2013 2012

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results) Presentation (6 results)

  • [Journal Article] Depletion of p62 reduces nuclear inclusions and paradoxically ameliorates disease phenotypes in Huntington's model mice.2015

    • Author(s)
      Kurosawa M, Matsumoto G, Kino Y, Okuno M, Kurosawa-Yamada M, Washizu C, Taniguchi H, Nakaso K, Yanagawa T, Warabi E, Shimogori T, Sakurai T, Hattori N, Nukina N.
    • Journal Title

      Hum Mol Genet

      Volume: 24 Pages: 1092-1105

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The estrogen receptor β-PI3K/Akt pathway mediates the cytoprotective effects of tocotrienol in a cellular Parkinson's disease model.2014

    • Author(s)
      Nakaso K, Tajima N, Horikoshi Y, Nakasone M, Hanaki T, Kamizaki K, Matsura T
    • Journal Title

      Biochim Biophys Acta (Mol Basis od Dis)

      Volume: 1842 Pages: 1303-1312

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The estrogen receptorβ-PI3K/Akt pathway mediates the cytoprotective effects of tocotrienol in a cellular Parkinson's disease model2014

    • Author(s)
      Nakaso K, Tajima N, Horikoshi Y, Nakasone M, Hanaki T, Kamizaki K, Matsura T
    • Journal Title

      Biochim Biophys Acta

      Volume: S0925-4439(14) Issue: 9 Pages: 95-97

    • DOI

      10.1016/j.bbadis.2014.04.008

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Deficiency of p62/Sequestosome 1 causes hyperphagia due to leptin resistance in the brain2013

    • Author(s)
      Harada H, Warabi E, Matsuki T, Yanagawa T, Okada K, Uwayama J, Ikeda A, Nakaso K, Kirii K, Noguchi N, Bukawa H, Siow R, Mann G, Shoda J, Ishii T, and Sakurai T.
    • Journal Title

      J. Neurosci.

      Volume: 33 Issue: 37 Pages: 14767-14777

    • DOI

      10.1523/jneurosci.2954-12.2013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dopamine-mediated oxidation of methionine 127 in α-synuclein causes cytotoxicity and oligomerization of α-synuclein.2013

    • Author(s)
      Nakaso K, Tajima N, Ito S, Teraoka M, Yamashita A, Horikoshi Y, Kikuchi D, Mochida S, Nakashima K and Matsura T
    • Journal Title

      PLOS ONE

      Volume: 8 Issue: 2 Pages: 1-9

    • DOI

      10.1371/journal.pone.0055068

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytoprotective effect of chlorogenic acid against α-synuclein-related toxicity in catecholaminergic PC12 cells2012

    • Author(s)
      Teraoka M, Nakaso K, Kusumoto C, Katano S, Tajima N, Yamashita A, Zushi T, Ito S and Matsura T
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 51 Issue: 2 Pages: 122-127

    • DOI

      10.3164/jcbn.D-11-00030

    • NAID

      130004879304

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] opamine-mediated oxidation of methionine 127 in alpha-synuclein causes cytotoxicity and oligomerization of alpha-synuclein.2014

    • Author(s)
      Kazuhiro Nakaso, Naoko Tajima, Yosuke Horikoshi, Satoru Ito, Tatsuya Matsura
    • Organizer
      SfN 44th Annual Meeting Neuroscience 2014
    • Place of Presentation
      Washington DC (米国)
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] ドパミン依存的なアルファシヌクレイン127番メチオニン残基の酸化修飾は神経毒性の原因となる2014

    • Author(s)
      中曽一裕,田島奈緒子,堀越洋輔,伊藤悟,松浦達也
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] パーキンソン病分子病態におけるαシヌクレイン酸化修飾と防御因子としてのメチオニンスルホキシド還元酵素2014

    • Author(s)
      中曽一裕,田島奈緒子,堀越洋輔,松浦達也
    • Organizer
      第67回日本酸化ストレス学会学術集会
    • Place of Presentation
      同志社大学良心館(京都市)
    • Year and Date
      2014-09-04 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Dopamine-mediated oxidation of methionine 127 in alpha-synuclein causes cytotoxicity and oligomerization of alpha-synuclein2014

    • Author(s)
      Kazuhiro Nakaso, Naoko Tajima, Yosuke Horikoshi, Tatsuya Matsura
    • Organizer
      SFRRI2014
    • Place of Presentation
      Kyoto(Kyoto International Conference Center)
    • Related Report
      2013 Research-status Report
  • [Presentation] パーキンソン病関連分子α-シヌクレインのメチオニン酸化修飾と細胞毒性2013

    • Author(s)
      中曽一裕,田島奈緒子,堀越洋輔,松浦達也
    • Organizer
      第66回日本酸化ストレス学会学術集会
    • Place of Presentation
      名古屋(ウインク愛知)
    • Related Report
      2013 Research-status Report
  • [Presentation] カテコールアミン酸化産物によるαシヌクレインのメチオニン酸化修飾とパーキンソン病の分子病態.2012

    • Author(s)
      中曽一裕,田島奈緒子,寺岡麻梨,山下敦,松浦達也
    • Organizer
      第65回日本酸化ストレス学会学術集会
    • Place of Presentation
      徳島県郷土文化会館(徳島)
    • Related Report
      2012 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi