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The search identification and functional analysis of the systemic humoral factor controlling Abeta accumulation in the brain

Research Project

Project/Area Number 19K16912
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionShiga University of Medical Science

Principal Investigator

Nakano Masaki  滋賀医科大学, 神経難病研究センター, 助教 (00823890)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsアルツハイマー病 / Amyloid-β / 老化 / 液性因子 / 並体結合 / アミロイドβ
Outline of Research at the Start

アルツハイマー病 (AD)の基本病態である脳内アミロイドβ(Aβ)蓄積の一次的原因ないし促進/抑制因子を、とくに老化関連液性因子の視点から探索し、発症前診断や先制治療の開発に貢献することを目的とする。アルツハイマー病の最大の危険因子は加齢つまり老化とされるが、『個体老化による何が脳内Aβ蓄積、引いてはアルツハイマー病発症に寄与するのか?』という 重大な問いは明らかになっていない。本研究では、ADモデルマウスと野生型マウスの老若個体を並体結合することにより、循環因子を共有させ、脳内Aβ蓄積に影響する全身性循環因子の存在を評価し、血液中より目的因子の同定を行う。

Outline of Final Research Achievements

In this study, we searched for primary cause and acceleration/inhibition factors of the amyloid β(Aβ) accumulation in the brain which was the basic pathology of Alzheimer's disease (AD) from the viewpoint of the particularly aging-related humoral factor. The purpose of this study was to contribute to presymptomatic diagnosis and development of the initiative treatment.
The existence of the systemic circulation factor which influenced the Aβ accumulation in the brain was suggested by the heterochronic parabiosis, a surgical model which results in shared circulation between the AD model mouse and the young or old individual of wild type mouse. In addition, we found candidate molecules which can control the Aβ accumulation in the brain by RNA sequence analysis.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病の治療法開発においては、臨床治験での多くの失敗を踏まえ、症状発現を指標とした治療から、発症前の脳内Aβ蓄積を指標とした先制治療への転換を迫られており、脳内Aβ蓄積の一次的要因を明らかにすることが一つの重要な課題である。しかし、これまでその知見は極めて乏しく先制治療実現の一つの障害になっている。加齢はアルツハイマー病に最大の危険因子であるが、その基盤となる分子メカニズムは未だ明らかにされていない。本研究による脳内Aβ蓄積を促進ないし抑制する全身性液性因子の存在の検証成果は、老化に伴うアルツハイマー病発症リスクのバイオマーカーやリスク介入の標的にもなる可能性を持つことが期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Transcriptional downregulation of FAM3C/ILEI in the Alzheimer’s brain.2022

    • Author(s)
      Watanabe N, Nakano M, Mitsuishi Y, Hara N, Mano T, Iwata A, Murayama S, Suzuki T, Ikeuchi T, Nishimura M
    • Journal Title

      Human Molecular Genetics

      Volume: 31 Issue: 1 Pages: 122-132

    • DOI

      10.1093/hmg/ddab226

    • NAID

      120007186913

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Potential Defense Mechanism Against Amyloid Deposition in Cerebellum2021

    • Author(s)
      Shahnur Alam, Masaki Nakano, Seiko Ishihara, Nobuto Kakuda, Tomohiro Miyasaka, Hina Uchiyama, Yuuna Shirai, Mohammad Moniruzzaman, Takashi Saito, Takaomi C. Saido, Masaki Nishimura, Satoru Funamoto
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 535 Pages: 25-32

    • DOI

      10.1016/j.bbrc.2020.12.036

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extracellular release of ILEI/FAM3C and amyloid-β is associated with the activation of distinct synapse subpopulations.2021

    • Author(s)
      Nakano M, Mitsuishi Y, Liu L, Watanabe N, Hibino E, Hata S, Saito T, Saido C T, Murayama S, Kasuga K, Ikeuchi K, Suzuki T, Nishimura M
    • Journal Title

      Journal of Alzheimer’s disease

      Volume: 80 Issue: 1 Pages: 159-174

    • DOI

      10.3233/jad-201174

    • NAID

      120007019774

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] FAM3C in Alzheimer’s disease. A risk-related molecule and potential therapeutic target.2020

    • Author(s)
      Nishimura M, Watanabe N, Hibino E, Nakano M, Mitsuishi Y, Liu L, Sugi T
    • Journal Title

      The Neuroscience of Dementia

      Volume: 2 Pages: 293-307

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Emodin, as a mitochondrial uncoupler, induces strong decreases in ATP levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve.2019

    • Author(s)
      Sugiyama, U., Shudo, T., Hosokawa, S., Watanabe, A., Nakano, M., Kakizuka, A.
    • Journal Title

      Genes to Cells

      Volume: 8 Issue: 8 Pages: 569-584

    • DOI

      10.1111/gtc.12712

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Extracellular release of ILEI/FAM3C and Aβ is associated with the activation of distinct synapse subpopulation2021

    • Author(s)
      Masaki Nakano, Yachiyo Mitsuishi, Lei Liu, Naoki Watanabe, Takashi Saito, Takaomi C Saido, Toshiharu Suzuki, Masaki Nishimura
    • Organizer
      AAIC2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ニコチン性アセチルコリン受容体刺激がAβ産生に与える影響2021

    • Author(s)
      中野 将希、斉藤 貴志、西道 隆臣、西村 正樹
    • Organizer
      第40回日本認知症学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Activation of distinct synaptic populations regulates extracellular release of ILEI/FAM3C and Aβ2020

    • Author(s)
      中野将希、三ツ石弥千代、渡邊直樹、日比野絵美、斉藤貴志、西道隆臣、鈴木利治、西村正樹
    • Organizer
      AAIC2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Aβ産生を抑制するFAM3C/ILEIは線虫において記憶学習に関連する2020

    • Author(s)
      中野 将希、杉 琢磨、西村 正樹
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] なぜAβ沈着は大脳で多く小脳で少ないのか?―小脳からの盛んなAβ排出ー2020

    • Author(s)
      Alam Shahnur、中野将希、石原聖子、宮坂知宏、角田伸人、斉藤貴志、西道隆臣、舟本 聡
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Presynaptic ILEI/FAM3C is released in an activity-dependent manner like Aβ exocytosis.2019

    • Author(s)
      中野将希、三ツ石弥千代、渡邊直希、日比野絵美、杉拓磨、斉藤貴志、西道隆臣、鈴木利治、西村正樹.
    • Organizer
      Neuro2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Synaptic activity-dependent release of presynaptic ilei/FAM3C.2019

    • Author(s)
      中野将希、三ツ石弥千代、渡邊直希、日比野絵美、斉藤貴志、西道隆臣、鈴木利治、西村正樹.
    • Organizer
      AAIC 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大脳皮質におけるILEI/FAM3CおよびAβの間質液への分泌様式に関する比較検討2019

    • Author(s)
      中野将希、三ツ石弥千代、渡邊直希、日比野絵美、斉藤貴志、西道隆臣、鈴木利治、西村正樹
    • Organizer
      第38回日本認知症学会学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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