Elucidation of the mechanism on the formation of early pathological lesion of prion diseases

2009 Fiscal Year Final Research Report

• Project/Area Number: 18208026
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Hokkaido University
• Principal Investigator: HORIUCHI Motohiro Hokkaido University, 大学院・獣医学研究科, 教授 (30219216)
• Co-Investigator(Kenkyū-buntansha): INANAMI Osamu 北海道大学, 大学院・獣医学研究科, 教授 (10193559) ; KIMURA Kazuhiro 北海道大学, 大学院・獣医学研究科, 教授 (30192561) ; OCHIAI Kenji 北海道大学, 大学院・獣医学研究科, 准教授 (80214162) ; HASEBE Rie 北海道大学, 大学院・獣医学研究科, 助教 (70431335) ; URYU Masahide (株)応用医学研究所, 研究員 (00399990) ; SON Chang-hyun 北海道大学, 大学院・獣医学研究科, 博士研究員 (70547786) ; OOSHIMA Masanobu 金沢大学, がん研究所, 教授 (40324610) ; FURUOKA Hidefumi 帯広畜産大学, 畜産学部, 教授 (60238665)
• Project Period (FY): 2006 – 2009
• Keywords: プリオン / DNAマイクロアレイ / 神経変性 / ミクログリア

Research Abstract

To identify host genes whose expression is up-regulated in the early stage of prion-infection, DNA microarray analysis was carried out and involvement of the genes in pathobiology of prion diseases was analyzed. The results showed that Cd14 molecule, known as receptor for LPS, influences the progression of the disease, whereas, Cxcl10, known as chemokine with neuroprotective effect, plays a role in antagonizing the disease progression. In addition, microglial activation was suggested to have a protective effect on the disease progression.

Research Products

• [Journal Article] Celldensity dependent increase of the amount of protease-resistant PrP in prion-infected Neuro2a mouse neuroblastoma cells. (2010)
  • Author(s): Nakamitsu, S., Kurokawa, A., Yamasaki, T., Uryu, M., Hasebe, R., Horiuchi, M.
  • Journal Title: J. Gen. Virol. 91 Pages: 563-569
  • Peer Reviewed
• [Journal Article] A novel copper(II) coordination at His186 in full-length murine prion protein. (2010)
  • Author(s): Watanabe, Y., Hiraoka, W., Igarashi, M., Ito, K., Shimoyama, Y., Horiuchi, M., Yamamori, T., Yasui, H., Kuwabara, M., Inagaki, F., Inanami, O.
  • Journal Title: Biochem. Biophys. Res. Commun. 394(3) Pages: 522-528
  • Peer Reviewed
• [Journal Article] Confomational Analysis of Soluble Oligomers of GFP Tagged Prion Protein by Fluorescence Fluctuation Spectroscopy (2010)
  • Author(s): Sakata, H., Horiuchi, M., Takahashi, I., Kinjo, M.
  • Journal Title: Curr. Pharm. Biotechnol. 11 Pages: 87-95
  • Peer Reviewed
• [Journal Article] Generation of monoclonal antibody that distinguishes PrPSc from PrPC and neutralizes prion infectivity. (2009)
  • Author(s): Horiuchi, M., Karino, A., Furuoka, H., Ishiguro, N., Kimura, K., Shinagawa, M.
  • Journal Title: Virology 394 Pages: 200-207
  • Peer Reviewed
• [Journal Article] The effect of transplantation of immortalized human bone marrow-derived mesenchymal stem cells on mice infected with prion. (2009)
  • Author(s): Song, C.-H., Honmou, O., Nakamura, K., Hamada, H., Furuoka, H., Hasebe, R., Horiuchi, M.
  • Journal Title: J. Virol. 83 Pages: 5918-5927
  • Peer Reviewed
• [Journal Article] The region approximately between amino acids 81 and 137 of proteinase K-resistant PrPSc is critical for the infectivity of the Chandler prion strain. (2009)
  • Author(s): Shindoh, R., Kim, C.-L., Song, C.-H., Hasebe, R., Horiuchi, M.
  • Journal Title: J. Virol. 83 Pages: 3852-3860
  • Peer Reviewed
• [Journal Article] Effect of intraventricular infusion of antiprion protein monoclonal antibodies on disease progression in prion-infected mice. (2008)
  • Author(s): Song, C.-H., Furuoka, H., Kim, C.-L., Ogino, M., Suzuki, A., Hasebe, R., Horiuchi, M.
  • Journal Title: J. Gen. Virol. 89 Pages: 1533-1544
  • Peer Reviewed
• [Presentation] Identification mAb 132 Rab 11 Merge Chandler Mock of chemotactic factors for migration of mice infected with prions. (2009)
  • Author(s): Song, C. -H., Honmou, O., Furuoka, H., Hasebe, R., Horiuchi, M.
  • Place of Presentation: Porto Carras, Greece.
  • Year and Date: 20090923-20090925
• [Presentation] Intracellular localization of abnormal isoform of prion protein. (2009)
  • Author(s): Horiuchi, M.
  • Organizer: "Prion and Virus Infections" BSJ & ABA Joint Symposium
  • Place of Presentation: Tokushima, Japan.
  • Year and Date: 2009-10-30
• [Presentation] 異常型プリオン蛋白の細胞内局在 (2009)
  • Author(s): 堀内基広
  • Organizer: 大阪大学蛋白質研究所セミナー
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-13
• [Presentation] Intracellular localization of disease-specific prion protein. (2009)
  • Author(s): Horiuchi, M., Yamasaki, T.
  • Organizer: Symposium on emerging and reemerging infectious diseases.
  • Place of Presentation: Tokyo, Japan.
  • Year and Date: 2009-02-17
• [Presentation] Pathology in guinea pig infected with bovine spongiform encephalopathy. (2008)
  • Author(s): Furuoka, H., Horiuchi, M., Sata T.
  • Place of Presentation: Madrid, Spain.
  • Year and Date: 20081006-20081008
• [Presentation] Prion propagation and its inhibition. (2007)
  • Author(s): Horiuchi, M.
  • Organizer: The 14th International Symposium for Zoonosis Control.
  • Place of Presentation: Sapporo, Japan.
  • Year and Date: 2007-10-31
• [Presentation] プリオンの増殖とその抑制 (2007)
  • Author(s): 堀内基広
  • Organizer: 第55回日本ウイルス学会
  • Place of Presentation: 札幌
  • Year and Date: 2007-10-22