| Project/Area Number |
25440064
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Biophysics
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
Ikura Teikichi 東京医科歯科大学, 難治疾患研究所, 准教授 (50251393)
|
|---|
| Project Period (FY) |
2013-04-01 – 2016-03-31
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | タウタンパク質 / プロリン異性化酵素 / 神経原線維変化 / 機能改変 / Pin1 / プロリン異性化 / 凝集化 / アルツハイマー病 / 脱リン酸化 / PP2A / リン酸化 / プロリン異性化活性 / 凝集 |
|---|
| Outline of Final Research Achievements |
The Alzheimer's disease-related protein, tau, aggregates into neurofibrillary tangles (NFT) when it is hyperphosphorylated. In this research project, I aimed to inhibit formation of TNF, stabilize microtubule, and furthermore prevent the Alzheimer's disease. In my strategy, I focused on the specific interactions between tau protein and peptidyl-prolyl isomerases (PPIases), Pin1 and FKBP12: PPIases restored the function of tau protein by presumably catalyzing isomerization of a specific pS/T-P or X-P motif. In this study, I introduced the comprehensive mutations at the active site of the PPIases and finally succeeded in discovery of several mutant proteins with higher activity than wild-type protein. Moreover, I tackled a functional change of Pin1 in which Pin1 was converted from a PPIase to a protease, and finally succeeded in creating a novel protease with the specificity to Proline residue including pS/pT-P motif of tau protein.
|
