• Top page
  • Timetable
  • Per session
  • Per presentation
  • How to
  • Meeting Planner



ポリグルタミン病、ALS、脊髄小脳変性症、その他の神経変性疾患 1
Polyglutamine Diseases, ALS, SCD, Other Neurodegenerative Disorder 1

開催日 2014/9/11
時間 9:00 - 10:00
会場 Room I(311+312)
Chairperson(s) 秦野 伸二 / Shinji Hadano (東海大学医学部基礎医学系分子生命科学 / Department of Molecular Life Sciences, Tokai University School of Medicine, Japan)
小野寺 理 / Osamu Onodera (新潟大学脳研究所 / Brain Research Institute, Niigata University, Japan)

Identification of target mRNA transported to axons by TDP-43

  • O1-I-1-2
  • 長野 清一 / Seiichi Nagano:1 廣川 祥子 / Sachiko Hirokawa:2 西澤 正豊 / Masatoyo Nishizawa:3 﨑村 建司 / Kenji Sakimura:4 小野寺 理 / Osamu Onodera:2 荒木 敏之 / Toshiyuki Araki:1 
  • 1:国立精神・神経医療研究センター・神経研・疾病研究第五部 / Dept PNS Research, Natl Inst of Neuroscience, NCNP, Tokyo, Japan 2:新潟大・脳研・分子神経疾患資源解析学 / Dept Molecular Neuroscience, Brain Research Inst, Niigata Univ, Niigata, Japan 3:新潟大・脳研・神経内科学 / Dept Neurology, Brain Research Inst, Niigata Univ, Niigata, Japan 4:新潟大・脳研・細胞神経生物学 / Dept Cellular Neurobiology, Brain Research Inst, Niigata Univ, Niigata, Japan 

PURPOSE: While abnormal deposition of TDP-43 is a hallmark in neurons of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusion bodies (FTLD-U), the pathogenic mechanism of the diseases by TDP-43 is largely unknown. TDP-43 is an RNA-binding protein that supposedly regulates transcription, splicing, nucleocytoplasmic export and transport of mRNA. We hypothesized that the failure of mRNA transport to axons by TDP-43 is associated with neurodegeneration in ALS and FTLD-U, and aimed to clarify the function of TDP-43 by identifying the target mRNA for TDP-43-mediated axonal transport.
METHODS: We detected mRNA decreased by shRNA-based TDP-43 down-regulation in axons of embryonic mouse cortical neurons using microarray analysis. We next analyzed the identified mRNA for binding and transport with TDP-43, localization, translation and function in axons.
RESULTS: Down-regulation of TDP-43 expression decreased mRNA of ribosomal proteins in axons. TDP-43 binds and transports the mRNA through their untranslated region. These mRNA were translated locally, and overall ribosomal function was suppressed in axons by the decreased expression of TDP-43.
DISCUSSION: In ALS and FTLD-U, neurodegeneration can arise from impaired protein synthesis in axons as a result of aggregation-mediated deficiency of transport of ribosomal protein mRNA by TDP-43. Further analysis will clarify the detailed molecular mechanisms.

Copyright © Neuroscience2014. All Right Reserved.