Genetic screen for disease-associated genes in glial cells using a novel Drosophila model of Alzheimer's disease

• Project/Area Number: 18K07517
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: Sekiya Michiko 国立研究開発法人国立長寿医療研究センター, 認知症先進医療開発センター, 室長 (40367412)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アルツハイマー病 / ショウジョウバエ / アミロイドベータ / グリア細胞 / アミロイドβペプチド / リスク遺伝子

Outline of Final Research Achievements

Alzheimer’s disease is a progressive neurodegenerative disease and is the main cause of senile dementia. Accumulated genetic studies suggest that a number of SNPs associated
with genes expressed in glial cells contribute to AD risk. To identify the glial genes that contribute to AD pathogenesis, we established a novel Drosophila model of Alzheimer’s disease and performed the genetic screen using this fly model.

Academic Significance and Societal Importance of the Research Achievements

高齢化の進む我が国において，認知症患者数の急増は深刻な社会問題であり，その原因であるアルツハイマー病の発症メカニズムの解明，治療薬標的の同定は急務である。本研究では，アルツハイマー病におけるグリア細胞機能の関与を解明する目的で，新規のアルツハイマー病モデルショウジョウバエを確立した。このモデルを用いることで，アルツハイマー病におけるグリア細胞機能の関与を解明すると共に，グリア細胞に着目した治療薬標的の同定が期待できる。また，既存のモデルとは異なる新しいシステムを有するモデルでの研究は，アルツハイマー病の発症機序の解明に新たな知見をもたらす可能性がある。

Research Products

• [Journal Article] Phenotypic analysis of a transgenic Drosophila model of Alzheimer’s amyloid-β toxicity (2021)
  • Author(s): M. Sekiya, K.M. Iijima
  • Journal Title: STAR Protocols Volume: - Issue: 2 Pages: 100501-100501
  • DOI: 10.1016/j.xpro.2021.100501
  • Peer Reviewed / Open Access
• [Journal Article] Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits, Key Regulators, and Potential Therapeutics for Alzheimer’s Disease (2021)
  • Author(s): Wang Minghui, Li Aiqun, Sekiya Michiko and et.al.
  • Journal Title: Neuron Volume: 109 Issue: 2 Pages: 257-272.e14
  • DOI: 10.1016/j.neuron.2020.11.002
  • Peer Reviewed / Open Access
• [Journal Article] Disruption of a RAC1-centred network is associated with Alzheimer's disease pathology and causes age-dependent neurodegeneration. (2020)
  • Author(s): Masataka Kikuchi, Michiko Sekiya, Norikazu Hara, Akinori Miyashita, Ryozo Kuwano, Takeshi Ikeuchi, Koichi M Iijima, Akihiro Nakaya
  • Journal Title: Human Molecular Genetics Volume: 29 Issue: 5 Pages: 817-833
  • DOI: 10.1093/hmg/ddz320
  • Peer Reviewed / Open Access
• [Presentation] Deficiency in a fly ortholog of HS-Aging related gene, sulfonylurea receptor/Sur, increased vulnerability to neurodegeneration in Drosophila models of Alzheimer’s disease (2020)
  • Author(s): Michiko Sekiya, Xiuming Quan, Yasufumi Sakakibara, Sachie Chikamatsu, Koichi M. Iijima
  • Organizer: Alzheimer's Association International Conference 2020
  • Int'l Joint Research
• [Presentation] 遺伝子ネットワーク解析を用いたアルツハイマー病の発症機序解明と創薬標的の探索 (2020)
  • Author(s): 関谷 倫子，Wang Minghui，榊原泰史，近松幸枝，Zhang Bin，飯島浩一
  • Organizer: 第93回日本生化学会大会
• [Presentation] アルツハイマー病におけるATP感受性K+チャネル機能の役割 (2020)
  • Author(s): 関谷倫子，権秀明，榊原泰史，近松幸枝，飯島浩一
  • Organizer: 第39 回日本認知症学会学術集会
• [Presentation] SULFONYLUREA RECEPTOR/SUR DEFICIENCY INCREASED VULNERABILITY TO NEURODEGENERATION IN DROSOPHILA MODELS OF ALZHEIMER’S DISEASE (2020)
  • Author(s): Michiko Sekiya, Xiuming Quan, Yasufumi Sakakibara, Sachie Chikamatsu, Koichi M. Iijima
  • Organizer: The 15th International Conference on Alzheimer’s and Parkinson’s Diseases (ADPD 2021)
  • Int'l Joint Research
• [Presentation] A Drosophila model of Alzheimer's disease (2019)
  • Author(s): Michiko Sekiya
  • Organizer: The 5th NCGG ICAH symposium
  • Int'l Joint Research / Invited
• [Presentation] A novel Drosophila model of Alzheimer’s disease (2019)
  • Author(s): Michiko Sekiya, Yasufumi Sakakibara, Sachie Chikamatsu, Koichi M. Iijima
  • Organizer: AAIC2019
  • Int'l Joint Research
• [Presentation] 新規アルツハイマー病モデルショウジョウバエの作製 (2019)
  • Author(s): 関谷倫子，榊原泰史，近松幸枝，飯島浩一
  • Organizer: 第38回日本認知症学会学術集会