Elucidation of the mechanisms of the prion protein misfolding

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05963
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Hokkaido University
• Principal Investigator: Kobayashi Atsushi 北海道大学, 獣医学研究院, 准教授 (50431507)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: プリオン / クロイツフェルト・ヤコブ病

Outline of Final Research Achievements

The M232R mutation of the PRNP gene, which is the causative mutation of a genetic prion disease, did not affect the GPI-anchoring, GPI-attachment site, GPI glycan structures, and brain distribution of prion proteins. Meanwhile, the M232R mutation increased the amount of prion proteins localized in mitochondria. The induction of mitochondrial distribution of prion proteins may accelerate the development of prion disease. This is the first time to show direct relationship between the mutation in the GPI-attachment signal peptide and development of disease. In addition, the present study revealed the detailed GPI glycan structures and the GPI-attachement site of human prion proteins for the first time.

Free Research Field

神経病理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、プリオン蛋白の遺伝子変異によって引き起こされる遺伝性プリオン病の発病メカニズムの一端を明らかにした。今後、その発病メカニズムを人工的に調節する方法をみつけることで、遺伝性プリオン病の発病を遅らせたり阻止したりすることが可能になると考えられる。また、遺伝性プリオン病以外のプリオン病においても同様の発病メカニズムが働いているのかを今後解析し、プリオン病全体の発病メカニズム解明につなげたい。