Elucidation of the mechanisms of the prion protein misfolding
| 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 |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | プリオン / クロイツフェルト・ヤコブ病 / GPIアンカー / 神経変性疾患 |
|---|
| 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.
|
| 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。
|
Report
(4 results)
Research Products
(31 results)
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Characterization of “sporadic CJD” with history of neurosurgery to identify potentially iatrogenic cases2019
Author(s)
Tsuyoshi Hamaguchi, Kenji Sakai, Atsushi Kobayashi, Tetsuyuki Kitamoto, Ryusuke Ae, Yosikazu Nakamura, Nobuo Sanjo, Kimihito Arai, Mizuho Koide, Fumiaki Katada, Masafumi Harada, Hiroyuki Murai, Shigeo Murayama, Tadashi Tsukamoto, Hidehiro Mizusawa, Masahito Yamada
Organizer
Asian Pacific Prion Symposium
Related Report
Int'l Joint Research
-
-
[Presentation] Characterization of “sporadic CJD” with history of neurosurgery to identify iatrogenic cases2018
Author(s)
Tsuyoshi Hamaguchi,1 Kenji Sakai,1 Atsushi Kobayashi,2 Tetsuyuki Kitamoto,3 Ryusuke Ae,4 Yosikazu Nakamura,4 Nobuo Sanjo,5 Kimihito Arai,6 Mizuho Koide,6 Fumiaki Katada,7 Masafumi Harada,8 Hiroyuki Murai,9 Shigeo Murayama,10 Tadashi Tsukamoto,10 Hidehiro Mizusawa,10 Masahito Yamada.1
Organizer
EuroCJD meeting 2018
Related Report
Int'l Joint Research / Invited
-
