Pathological analysis of PAD and citrullinated proteins that triggers the onset of Alzheimer's disease

• Project/Area Number: 21590392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: HANDA Setsuko 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, 助手 (30360697)
• Co-Investigator(Kenkyū-buntansha): 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, 研究副部長 (50270658)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 脳・神経 / アルツハイマー病 / シトルリン化 / PAD / プロテオーム / 診断薬

Research Abstract

The abnormal accumulation of citrullinated proteins were detected in the brain from Alzheimer's disease(AD) patients. By using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, two of the citrullinated proteins were identified as a vimentin and a glial fibrillary acidic protein(GFAP). In addition, we constructed a ELISA system which detect the citrullinated GFAP to develop diagnostic laboratory tests for early diagnosis of AD.

Research Products

• [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, B., Jeon, Y. C., Choi, J. K., Park, M., Kim, J. I., Ishigami, A., Maruyama, N. Carp, R. I., Kim, Y. S., Choi, E. K
  • Journal Title: Biochem. J Volume: 445 Issue: 2 Pages: 183-192
  • DOI: 10.1042/bj20120025
  • Peer Reviewed
• [Journal Article] Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice (2011)
  • Author(s): Coudane, F., Mechin, M. C., Huchenq, A., Henry, J., Nachat, R., Ishigami, A., Adoue, V., Sebbag, M., Serre, G., Simon, M
  • Journal Title: Eur. J. Dermatol Volume: 21 Pages: 376-384
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21697043
  • Peer Reviewed
• [Journal Article] Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice : nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins (2011)
  • Author(s): Jang, B., Shin, HY., Choi, JK., Nguyen, du PT., Jeong, BH., Ishigami, A., Maruyama, N., Carp, RI., Kim, YS., and Choi, EK
  • Journal Title: J. Neuropathol. Exp. Neurol Volume: 70 Issue: 2 Pages: 116-124
  • DOI: 10.1097/nen.0b013e318207559e
  • Peer Reviewed
• [Journal Article] Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice : nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins (2011)
  • Author(s): Jang, et.al.
  • Journal Title: J.Neuropathol.Exp.Neurol. Volume: 70 Pages: 116-124
  • Peer Reviewed
• [Journal Article] Deimination and expression of peptidylarginine deiminases during cutaneous wound healing in mice (2011)
  • Author(s): Coudane, et.al.
  • Journal Title: Eur.J.Dermatol. Volume: 21 Pages: 376-384
  • Peer Reviewed
• [Journal Article] Involvement of peptidylarginine deiminase-mediated posttranslational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease (2010)
  • Author(s): Jang, B., Jin, JK., Jeon, YC., Cho, HJ., Ishigami, A., Choi, KC. Carp, RI
  • Journal Title: Acta Neuropatho Volume: 119 Issue: 2 Pages: 199-210
  • DOI: 10.1007/s00401-009-0625-x
  • Peer Reviewed
• [Journal Article] (REVIEW ARTICLE) Importance of research on peptidylarginine deiminase and citrullinated proteins in age-related disease (2010)
  • Author(s): Ishigami, A. and Maruyama, N
  • Journal Title: Geriatr : Gerontol. Int Volume: 10 Issue: s1 Pages: 53-58
  • DOI: 10.1111/j.1447-0594.2010.00593.x
  • Peer Reviewed
• [Journal Article] Developmental and age related changes of peptidylarginine deiminase 2 in the mouse brain (2010)
  • Author(s): Shimada, et al.
  • Journal Title: J.Neurosci.Res. Volume: 88 Pages: 798-806
  • Peer Reviewed
• [Journal Article] Importance of research on peptidylarginine deiminase and citrullinated proteins in age related disease (2010)
  • Author(s): Ishigami, et al.
  • Journal Title: Geriatr.Gerontol.Int. Volume: 10(Sup.1)
  • NAID: 10027273021
  • Peer Reviewed
• [Journal Article] Over-expression of Senescence Marker Protein-30 Decreases Reactive Oxygen Species in Human Hepatic Carcinoma Hep G2 cells (2009)
  • Author(s): Handa, S., Maruyama, N. and Ishigami, A.
  • Journal Title: Biol. Pharm. Bull Volume: 32 Pages: 1645-1648
  • NAID: 130000116921
  • URL: http://dx.doi.org/10.1248/bpb.32.1645
  • Peer Reviewed
• [Journal Article] Elevated levels of 4-hydroxynonenal-histidine Michael adduct in the hippocampi of patients with Alzheimer's disease (2009)
  • Author(s): Fukuda, M., Kanou, F., Shimada, N., Sawabe, M., Saito, Y., Murayama, S., Hashimoto, M., Maruyama, N. and Ishigami, A
  • Journal Title: Biomed. Res Volume: 30 Pages: 227-233
  • NAID: 130004903756
  • URL: http://dx.doi.org/10.2220/biomedres.30.227
  • Peer Reviewed
• [Journal Article] Senescence marker protein 30 is up-regulated in kainate-induced hippocampal damage through ERK-mediated astrocytosis (2009)
  • Author(s): Son, T. G., Park, H. R., Kim, S. J., Kim, K., Kim, MS., Ishigami, A., Handa, S., Maruyama, N. Chung, H. Y. and Lee, J
  • Journal Title: J. Neurosci. Res Volume: 87 Issue: 13 Pages: 2890-2897
  • DOI: 10.1002/jnr.22122
  • Peer Reviewed
• [Journal Article] Senescence marker protein 30 is up-regulated in kainate-induced hippocampal damage through ERK-mediated astrocytosis (2009)
  • Author(s): Son, et.al.
  • Journal Title: J.Neurosci.Res. 87 Pages: 2890-2897
  • Peer Reviewed
• [Journal Article] Over-expression of Senescence Marker Protein-30 Decreases Reactive Oxygen Species in Human Hepatic Carcinoma Hep G2 cells (2009)
  • Author(s): Handa, et.al.
  • Journal Title: Biol.Pharm.Bull. 32 Pages: 1645-1648
  • NAID: 130000116921
  • Peer Reviewed
• [Journal Article] Elevated levels of 4-hydroxynonenal-histidine Michael adduct in the hippocampi of patients with Alzheimer's disease (2009)
  • Author(s): Fukuda, et al.
  • Journal Title: Biomed.Res. 30 Pages: 227-233
  • Peer Reviewed
• [Presentation] アルツハイマー病治療薬を指向したアミロイドベータ凝集阻害剤の開発:アリールベンゾフラン誘導体 (2011)
  • Author(s): 鈴木英治、今井雅之、松山明弘、奥野友哉梨、中越雅道、石神昭人、氷川英正、横山祐作
  • Organizer: 第131回日本薬学会
  • Place of Presentation: 静岡
• [Presentation] アルツハイマー病治療薬を指向したアミロイドベータ凝集阻害剤の開発:アリールベンゾフラン誘導体 (2011)
  • Author(s): 鈴木英治, 他
  • Organizer: 日本薬学会
  • Place of Presentation: 静岡
• [Presentation] ストレスによるマウス血漿総抗酸化能、抗酸化物質濃度の変化 (2010)
  • Author(s): 人見嘉哲、辻本藤太郎、石神昭人、近藤嘉高、神林康弘、弘田量二、日比野由利、柴田亜樹、中村裕之
  • Organizer: 第9回分子予防環境医学研究会
  • Place of Presentation: 東京
• [Presentation] 関節リウマチにおける血漿ペプチジルアルギニンデイミナーゼ4(PAD4)及び抗PAD4抗体 (2009)
  • Author(s): 木村直樹、杉原毅彦、石神昭人
  • Organizer: 第53回日本リウマチ学会総会・学術総会
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.aging-regulation.jp/kenkyu/pad-02.html
• [Remarks]
  • URL: http://www.aging-regulation.jp/kenkyu/pad-02.html