| Project/Area Number |
08458259
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neuroscience in general
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
ISHIURA Shoichi The University of Tokyo, Institute of Molecular and Cellular Biosciences, Associate Professor, 分子細胞生物学研究所, 助教授 (10158743)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SORIMACHI Hiroyuki The University of Tokyo, Institute of Molecular and Cellular Biosciences, Assist, 分子細胞生物学研究所, 助手 (10211327)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥4,700,000 (Direct Cost: ¥4,700,000)
|
|---|
| Keywords | Alzheimer's disease / Amyloid / Protease / Signal molecules / Processing / Secretion / ソーティング |
|---|
| Research Abstract |
Alzheimer's disease amyloid precursor protein (APP) has attracted attention due to its involvement in the deposition of amyloid beta protein found in brain of both sporadic and genetic Alzheimer's disease patients. It is accepted that APP undergoes tow different types of processing catalyzed by three hypothesized proteases. One type mediated by alpha-secretase involves the non-amyloidogenic pathway, which precludes the generation of the beta protein. The N-terminal large fragment of APP is secreted into serum.
The intracellular sorting of APP has attracted much interest, because some sorting signals in APP molecule are highly involved in the fate of newly-synthesized APP.We constracted two mutants, APPE19 and APPdeltaC10, which contains or deletes an endoplasmic reticulum (ER) retention signal. Addition of ER retention signal inhibied secretion of APP,while deletion of it promoted secretion. These results suggest that these sequences are important for the secretion and intracellular metabolism of APP.
|
