The possibility of new prion binding protein in the therapeutic development for prion diseases.

• Project/Area Number: 26670229
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Yamagoe Satoshi 国立感染症研究所, 真菌部, 主任研究官 (00212283)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: プリオン結合タンパク質 / ブリオン病 / 遺伝子改変マウス / プリオン病 / 新規結合蛋白質 / LECT2 / プリオン / 脳神経疾患

Outline of Final Research Achievements

Prion diseases are fatal transmissible neurodegenerative disorders and characterized by an accumulation of disease-associated forms of prion protein in the central nervous system. We identified a novel prion binding protein, designated PBP, physically associated with cellular prion protein. As the mechanism of infectivity involves a change in the normal cellular form into disease-associated forms, we speculated the possibility that PBP affected this conversion to influent the development of prion diseases. To test this, we have used the mouse model of prion diseases in PBP deficient mouse and PBP transgenic mouse. We found that the expression levels of PBP were correlated with the progression of the desease.

Research Products

• [Journal Article] Crystal Structure of Human Leukocyte Cell-derived Chemotaxin 2 (LECT2) Reveals a Mechanistic Basis of Functional Evolution in a Mammalian Protein with an M23 Metalloendopeptidase Fold (2016)
  • Author(s): Hai Zheng, Takuya Miyakawa, Yoriko Sawano, Atsuko Asano, Akinori Okumura, Satoshi Yamagoe, Masaru Tanokura
  • Journal Title: Journal of Biological Chemistry Volume: 291 Issue: 33 Pages: 17133-17142
  • DOI: 10.1074/jbc.m116.720375
  • Peer Reviewed
• [Journal Article] Reduced serum levels of leukocyte cell-derived chemotaxin 2 are associated with the presence of diabetic retinopathy (2016)
  • Author(s): Akinori Okumura, Hiroyuki Unoki-Kubota, Natsuyo Yoshida-Hata, Ritsuko, Yamamoto-Honda, Shigeo Yamashita, Minoru Iwata, Kazuyuki Tobe, Hiroshi Kajio, Mitsuhiko Noda, Naomichi Katai, Satoshi Yamagoe, Yasushi Kaburagi
  • Journal Title: Clinica Chimica Acta Volume: 463 Pages: 145-149
  • DOI: 10.1016/j.cca.2016.10.031
  • Peer Reviewed
• [Journal Article] LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance (2014)
  • Author(s): Fei Lan, H Misu, K Chikamoto, H Takayam, A Kikuchi, K Mohri, N Takata, H Hayashi, N Matsuzawa-Nagata, Y Takeshita, H Noda, Y Matsumoto, T Ota, T Nagano, M Nakagen, K Miyamoto, K Takatsuki, T Seo, K Iwayama, K Tokuyama, S Matsugo, H Tang, Y Saito, S Yamagoe, S Kaneko, T Takamura
  • Journal Title: Diabete Volume: 63 Issue: 5 Pages: 1649-1664
  • DOI: 10.2337/db13-0728
  • Peer Reviewed / Open Access
• [Remarks] LECT2に関する研究
  • URL: http://www.geocities.jp/lect2_yamagoe/