Elucidation of the prion pathogenic decision mechanism through a copper ion binding site of a prion protein

• Project/Area Number: 25870479
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology; Veterinary medical science
• Research Institution: The University of Tokushima
• Principal Investigator: HARA Hideyuki 徳島大学, 疾患酵素学研究センター, 助教 (40469953)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: プリオン / 構造変換 / 銅イオン / オクタペプチドリピート / OR / リピート部位 / 銅 / 神経変性 / クロイツフェルト・ヤコブ病 / 狂牛病 / スクレイピー

Outline of Final Research Achievements

Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrPSc; PrP refers to prion protein). Structural conversion of the normal cellular isoform, designated PrPC, into PrPSc is a key event in prion propagation. However, the conversion mechanism remains unclear. In this study, we intracerebrally inoculated prions into tg(PrPΔOR)/Prnp0/0 mice, which express mouse PrP missing only the octapeptide repeat (OR) region on the PrP-null background. There are different incubation time in infected the prions. As a result, the mechanism of structural conversion was depending on the type of prions. Also we examined the effects of copper ions on the pathological progression of prion disease. However, copper ions didn't have any influence on the pathological progression.

Research Products

• [Journal Article] Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice. (2014)
  • Author(s): Uchiyama K, Miyata H, Yano M, Yamaguchi Y, Imamura M, Muramatsu N, Das NR, Chida J, Hara H, Sakaguchi S.
  • Journal Title: PLoS One Volume: 9 Issue: 10 Pages: e109737-e109737
  • DOI: 10.1371/journal.pone.0109737
  • Peer Reviewed / Open Access
• [Journal Article] Species-barrier phenomenon in prion transmissibility from a viewpoint of protein science (2013)
  • Author(s): Hagiwara, K., Hara, H., and Hanada, K.
  • Journal Title: J. Biochem. Volume: 153 Issue: 2 Pages: 139-145
  • DOI: 10.1093/jb/mvs148
  • NAID: 40019566388
  • Peer Reviewed
• [Journal Article] 「プリオン仮説」の最終証明に挑戦しませんか？ (2013)
  • Author(s): 原 英之
  • Journal Title: 生物工学会誌 Volume: 91 Pages: 471-471
• [Presentation] 超好熱菌由来プロテアーゼによるプリオンタンパク質分解の評価 (2014)
  • Author(s): 清水 七海、古賀 雄一、作道 章一、原 英之、坂口 末廣、金谷 茂則
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都国際会館（京都府・京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 超好熱菌由来プロテアーゼによるプリオンタンパク質分解の評価 (2014)
  • Author(s): 古賀 雄一、清水 七海、作道 章一、原 英之、坂口 末廣、金谷 茂則
  • Organizer: 第66回日本生物工学会大会,
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2014-09-09 – 2014-09-11