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Neuronal activity affects AD pathophysiology

Research Project

Project/Area Number 16K09669
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Kasuga Kensaku  新潟大学, 脳研究所, 助教 (70547546)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアルツハイマー病 / Alzheimer's disease / 神経活動 / neuronal activation / APP processing / Aβ / NMDA受容体 / neuronal activity / APPプロセッシング / アミロイド前駆体蛋白 / アミロイドβ / mRNA / ネットワーク
Outline of Final Research Achievements

To clarify the association between Alzheimer's pathophysiology and neuronal activity, we analyzed the processing of amyloid precursor protein (APP) under various conditions of glutamatergic activation using primary culture of rat cortical neurons. At 100 μM glutamate, the expression of full-length APP transiently decreased after 2 hours of activation, with decreased APP C-terminal fragment β (CTFβ). In contrast, at 0.1 μM glutamate, the expression of CTFβ increased after 2 hours activation, and levels of Aβ elevated after 24 hours activation. Furthermore, this elevation of Aβ was suppressed by inhibiting the NMDA receptor. These results suggest that suppression of sustained neural activation would be a novel therapeutic target for Alzheimer's disease.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病 (AD) の主要な病理変化の一つは神経細胞外に沈着するβ-アミロイド (Aβ)から構成される老人斑である.
本研究は,持続的な神経細胞の興奮がAβ産生亢進を介しAD病態に関与することを示した.さらに,NMDA受容体の阻害によりAβ産生を抑制することを明らかにしたことから,持続的な神経興奮の抑制がADの新たな治療ターゲットとなることが示唆された.

Report

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

    (4 results)

All 2019 2018 2017

All Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] TIME- AND EXTENT- DEPENDENT EFFECT OF NEURONAL ACTIVATION ON Β-AMYLOID PRECURSOR PROTEIN (APP) PROCESSING2019

    • Author(s)
      Ishiguro T, Kasuga K, Saito K, Mezaki N, Miura T, Tokutake T, Onodera O, Ikeuchi T
    • Organizer
      The 14th International Conference on Alzheimer's & Parkinson's Diseases
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経細胞興奮がβ-amyloid precursor protein(APP)processingへ及ぼす影響2018

    • Author(s)
      石黒敬信、春日健作、斎藤健智、目﨑直実、三浦健、小野寺理、池内健
    • Organizer
      第37回日本認知症学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経細胞興奮がβ-amyloid precursor protein (APP) processingへ及ぼす影響2017

    • Author(s)
      石黒敬信, 春日健作, 斎藤健智, 目﨑直実, 三浦健, 小野寺理, 池内健
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] THE EFFECT OF NEURONAL ACTIVITY ON Β-AMYLOID PRECURSOR PROTEIN (APP) PROCESSING IN CULTURED CELLS2017

    • Author(s)
      Ishiguro T, Kasuga K, Saito K, Mezaki N, Miura T, Onodera O, Ikeuchi T
    • Organizer
      World Congress of Neurology 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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