Development of diagnostic agent for dementia

• Project/Area Number: 24659169
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: ISHIGAMI Akihito 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (50270658)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 認知症 / 臨床検査試薬 / アルツハイマー病 / 老化 / シトルリン化タンパク質

Outline of Final Research Achievements

Peptidylarginine deiminases (PADs) are post-translational modification enzymes that citrullinate protein arginine residues. Abnormal protein citrullination by PAD2 has been closely associated with the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD). In this study, we tried to develop a novel method for sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of citrullinated proteins which may become a useful marker of human neurodegenerative diseases.

Research Products

• [Journal Article] Peptidylarginine deiminase and protein citrullination in prion diseases: Strong evidence of neurodegeneration. (2013)
  • Author(s): Jang, B., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Journal Title: Prion Volume: 7 Issue: 1 Pages: 42-46
  • DOI: 10.4161/pri.22380
  • Peer Reviewed
• [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis. (2013)
  • Author(s): Ishigami, A., Uchida, Y., Miyazaki, T., Handa, S., Choi, E.K,, Kim, Y.S,, Kasahara, Y., Maruyama, N.
  • Journal Title: Mod Rheumatol. Volume: 23 Issue: 4 Pages: 794-803
  • DOI: 10.1007/s10165-012-0748-0
  • NAID: 10031189176
  • Peer Reviewed
• [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis. (2012)
  • Author(s): Ishigami et al.
  • Journal Title: Mod Rheumatol. Volume: in press
  • NAID: 10031189176
  • Peer Reviewed
• [Journal Article] Peptidylarginine deiminase modulates the physiological roles of enolase via citrullination: links between altered multifunction of enolase and neurodegenerative diseases. (2012)
  • Author(s): Jang et al.
  • Journal Title: Biochem. J. Volume: 445 Pages: 183-192
  • Peer Reviewed
• [Presentation] シトルリン化タンパク質特異的モノクローナル抗体の作製と特異性の解析 (2014)
  • Author(s): 加賀美弥生、丸山直記、石神昭人
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] ヒトグリオーマ細胞株U-251MG細胞でのPAD2誘導に伴うシトルリン化タンパク質の増加 (2014)
  • Author(s): 増冨裕文、下門顕太郎、石神昭人
  • Organizer: 第37回 日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] ヒトグリオーマ細胞株U-251MG細胞におけるcAMPによるPAD2の誘導 (2014)
  • Author(s): 増冨裕文、下門顕太郎、丸山直記、石神昭人
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] PADI4測定系の確立と臨床応用 (2014)
  • Author(s): 石神昭人
  • Organizer: 第58回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24
  • Invited
• [Presentation] Age-related changes of peptidylarginine deiminase 2 in the mouse brain. (2013)
  • Author(s): Kagami, Y., Shimada, N., Handa, S., Choi, E.K., Kim, Y.S., Ito, H., Maruyama, N., Ishigami, A.
  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics (IAGG 2013)
  • Place of Presentation: Seoul, Korea
• [Presentation] Peptidylarginine deiminase 2-mediat ed protein citrullinati on in prion disease. (2013)
  • Author(s): Kim, H.J., Jang, B., Jin, J.K., Jeon, Y.C., Ishigami, A., Maruyama, N., Carp, R.I., Kim, Y.S., Choi, E.K.
  • Organizer: The 20th IAGG World Congress of Gerontology and Geriatrics (IAGG 2013)
  • Place of Presentation: Seoul, Korea
• [Presentation] 腫瘍組織におけるシトルリン化タンパク質の局在と病態との相関. (2012)
  • Author(s): 加賀美弥生 他
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] 関節リウマチの早期診断を目指した新規hPAD4測定法及びhPAD4自己抗体検出法の確立. (2012)
  • Author(s): 半田節子 他
  • Organizer: 第85回日本生化学大会
  • Place of Presentation: 福岡
• [Book] Ishigami, A. Choi, E.K., Kim, Y.S., Maruyama, N. (2014)
  • Author(s): Deimination in Alzheimer’s Disease. In: Protein Deimination in Human Health and Disease.
  • Total Pages: 433
  • Publisher: Springer
• [Book] Deimination in Prion Diseases. In: Protein Deimination in Human Health and Disease. (2014)
  • Author(s): Choi, E.K., Jang, B., Ishigami, A., Maruyama, N., Carp, R.I.,Kim, Y.K.
  • Total Pages: 433
  • Publisher: Springer
• [Remarks] 分子老化制御
  • URL: http://www.aging-regulation.jp
• [Remarks] 老化制御研究チーム 分子老化制御
• [Remarks] http://www.aging-regulation.jp/