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

Neuro-epigenetics for the discover of novel pathomechanism of neurodegeneration.

Research Project

Project/Area Number 16H05319
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionThe University of Tokyo

Principal Investigator

Iwata Atsushi  東京大学, 医学部附属病院, 准教授 (40401038)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsエピゲノム / アルツハイマー病 / ヒストン修飾 / 発現変化 / エピジェネティクス / 神経変性疾患 / レビー小体病 / KIi-ALS PD complex / BRCA1 / FGFR3 / 認知症 / メチル化
Outline of Final Research Achievements

We challenged how we could use the diseased brain to extract information that might be specific and important to the disease. We performed indirect transcriptome analysis by purifying neuronal nuclei and extracting epigenome information from them as a methodology that enables resistance to postmortem changes and neural cell specific information extraction. By using this method, we were able to approach a new pathological condition of Alzheimer's disease. In other words, the function of DNA repair protein BRCA1 in nerve cells was reduced, which resulted in the reduction of nerve cell function. By applying this method, we performed neural cell-specific analysis of histone modification and found that expression changes of genes related to Alzheimer's disease are controlled by epigenetic.

Academic Significance and Societal Importance of the Research Achievements

全く新しい方法論を用いて剖検脳を用いることによって神経細胞内の遺伝子発現環境を推定,解析する方法論を確立し,それによる疾患特異的遺伝子発現異常を捉えることに成功した.これにより,アルツハイマー病の疾患発症メカニズムのより深い理解へとつながり,更には新規治療方法論の立案の一助となった.本本法論は,疾患脳発の情報抽出,すなわちボトムアップによる疾患理解という新しい疾患解析法となった.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Chronic cerebral hypoperfusion shifts the equilibrium of amyloid β oligomers to aggregation-prone species with higher molecular weight2019

    • Author(s)
      Bannai Taro、Mano Tatsuo、Chen Xigui、Ohtomo Gaku、Ohtomo Ryo、Tsuchida Takeyuki、Koshi-Mano Kagari、Hashimoto Tadafumi、Okazawa Hitoshi、Iwatsubo Takeshi、Tsuji Shoji、Toda Tatsushi、Iwata Atsushi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2827-2827

    • DOI

      10.1038/s41598-019-39494-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cilostazol alleviates white matter degeneration caused by chronic cerebral hypoperfusion in mice: Implication of its mechanism from gene expression analysis2018

    • Author(s)
      Ohtomo Ryo、Bannai Taro、Ohtomo Gaku、Shindo Akihiro、Tomimoto Hidekazu、Tsuji Shoji、Iwata Atsushi
    • Journal Title

      Neuroscience Letters

      Volume: 662 Pages: 247-252

    • DOI

      10.1016/j.neulet.2017.10.045

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA methylation level of the neprilysin promoter in Alzheimer's disease brains2018

    • Author(s)
      Nagata Kenichi、Mano Tatsuo、Murayama Shigeo、Saido Takaomi C.、Iwata Atsushi
    • Journal Title

      Neuroscience Letters

      Volume: 670 Pages: 8-13

    • DOI

      10.1016/j.neulet.2018.01.003

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methylation changes and aberrant expression of FGFR3 in Lewy body disease neurons2018

    • Author(s)
      Tsuchida Takeyuki、Mano Tatsuo、Koshi-Mano Kagari、Bannai Taro、Matsubara Tomoyasu、Yamashita Satoshi、Ushijima Toshikazu、Nagata Kenichi、Murayama Shigeo、Toda Tatsushi、Tsuji Shoji、Iwata Atsushi
    • Journal Title

      Brain Research

      Volume: 1697 Pages: 59-66

    • DOI

      10.1016/j.brainres.2018.06.017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of subclinical carotid atherosclerosis with immediate memory and other cognitive functions2017

    • Author(s)
      Matsumoto Lumine、Suzuki Kazushi、Mizuno Yoshiko、Ohike Yumiko、Ozeki Atsuko、Ono Satoshi、Takanashi Mikio、Sawaki Daigo、Suzuki Toru、Yamazaki Tsutomu、Tsuji Shoji、Iwata Atsushi
    • Journal Title

      Geriatrics & Gerontology International

      Volume: 18 Issue: 1 Pages: 65-71

    • DOI

      10.1111/ggi.13142

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuron-specific methylome analysis reveals epigenetic regulation and tau-related dysfunction of BRCA1 in Alzheimer’s disease2017

    • Author(s)
      Mano Tatsuo、Nagata Kenichi、Nonaka Takashi、Tarutani Airi、Imamura Tomohiro、Hashimoto Tadafumi、Bannai Taro、Koshi-Mano Kagari、Tsuchida Takeyuki、Ohtomo Ryo、Takahashi-Fujigasaki Junko、Yamashita Satoshi、Ohyagi Yasumasa、Yamasaki Ryo、Tsuji Shoji、Tamaoka Akira、et al.
    • Journal Title

      Proc Natl Acad Sci U.S.A.

      Volume: 114 Issue: 45

    • DOI

      10.1073/pnas.1707151114

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Tau-related dysfunction of BRCA1 lead to reduced neuronal plasticity in Alzheimer's disease2018

    • Author(s)
      Tatsuo Mano, Atsushi Iwata, Takashi Nonaka, Airi Tarutani, Tadafumi Hashimoto, Masato Hasegawa, Takeshi Iwatsubo, Tatsushi Toda
    • Organizer
      American Academy of Neurology 70th Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neuron-specific histone modification analysis of sporadic Alzheimer’s disease2018

    • Author(s)
      Kagari Mano, Tatsuo Mano, Atsushi Iwata, Shigeo Murayama, Tatsushi Toda
    • Organizer
      AAIC 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Tau-related dysfunction of BRCA1 lead to reduced neuronal plasticity in Alzheimer's disease2018

    • Author(s)
      Tatsuo Mano, Atsushi Iwata, Takashi Nonaka, Airi Tarutani, Tadafumi Hashimoto, Masato Hasegawa, Takeshi Iwatsubo, Tatsushi Toda
    • Organizer
      AAIC 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro AD model with human neuronal progenitor cells demonstrates BRCA1 involvement in DNA repair in differentiated neuronal cells.2017

    • Author(s)
      Tatsuo Mano, Atsush Iwata
    • Organizer
      23th World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of Neuron-specific histone modifications.2017

    • Author(s)
      Kagari Koshi-Mano, Tatsuo Mano, Atsushi Iwata
    • Organizer
      23th World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chronic cerebral hypoperfusion accelerates amyloid beta deposits in APP/PS1 transgenic mice.2017

    • Author(s)
      Taro Bannai, Ryo Ohtomo, Tatsuo Mano, Shoji Tsuji, Atsushi Iwata
    • Organizer
      23th World Congress of Neurology
    • Related Report
      2017 Annual Research Report
  • [Presentation] エピゲノム解析を通じたアルツハイマー病の新規病態の解明2017

    • Author(s)
      岩田淳
    • Organizer
      第39回日本生物学的精神医学会,第47回日本神経精神薬理学
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Neuron-specific methylome analysis reveals new pathomechanism in Alzheimer’s disease brains.2017

    • Author(s)
      Atsushi Iwata
    • Organizer
      Neuro2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 神経細胞特異的DNAメチル化解析によるアルツハイマー病の病態分子探索とその機能的意義2016

    • Author(s)
      間野達雄,永田 健一,村山 繁雄,西道 隆臣,辻 省次,岩田 淳
    • Organizer
      第10回日本エピジェネティクス研究会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
  • [Presentation] Epigenetic regulation of BRCA1 in Alzheimer’s disease. Evaluation of post-mortem brain and model mice reveals importance of aggregated tau.2016

    • Author(s)
      Atsushi Iwata
    • Organizer
      AAIC (Alzheimer’s association International Conference)
    • Place of Presentation
      Toronto, ON, Canada
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neuron-specific methylome analysis reveals new pathomehanism in Alzheimer’s disease brains.2016

    • Author(s)
      Tatsuo Mano, Atsushi Iwata
    • Organizer
      AAIC (Alzheimer’s association International Conference)
    • Place of Presentation
      Toronto, ON, Canada
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] プレス発表

    • URL

      http://www.h.u-tokyo.ac.jp/press/press_srchives/20171017.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi