| Project/Area Number |
12210021
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | NATIONAL INSTITUTE FOR LONGEVITY SCIENCES (2002-2004)
National Center of Neurology and Psychiatry (2000-2001) |
|---|
Principal Investigator |
TABIRA Takeshi NATIONAL INSTITUTE FOR LONGEVITY SCIENCES, DIRECTOR GENERAL, (研究所), 研究所長 (80112332)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANAKA Shin ANIMAL FACILITY FOR AGING RESEARCH, NATIONAL INSTITUTE FOR LONGEVITY SCIENCES, SECTION CHIEF, 研究所, 室長 (70134624)
ARAKI Wataru DEPARTMENT OF DEMYELINATING DISEASE AND AGING, NATIONAL INSTITUTE OF NEUROSCIENCE, SECTION CHIEF, 神経研究所, 室長 (60311429)
原 英夫 国立精神・神経センター, 神経研究所・6部, 室長 (00260381)
高橋 慶吉 国立精神・神経センター, 神経研究所・6部, 室長 (40117148)
|
|---|
| Project Period (FY) |
2000 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥55,600,000 (Direct Cost: ¥55,600,000)
Fiscal Year 2004: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2003: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2002: ¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2001: ¥19,600,000 (Direct Cost: ¥19,600,000)
|
|---|
| Keywords | Alzheimer's disease / β amyloid / apoptosis / glypican 1 / neprilysin / aging / adoplin / AB-DIP / アミロイド / β蛋白 / グリピカン / ラフト / PS1 / PS2 / APP / DRAL / LIM / Alzheimer |
|---|
| Research Abstract |
1.We identified glypican-1 as an Aβ-binding protein. Glypican-1 was enriched in the raft fraction, and deposited in senile plaques. Glypican-1 enhanced Aβ-induced cell death.
2.By using the differential display between PS1 wild and mutant cell lines, we identified a novel protein, adoplin. Adoplin was a membrane protein, and made a complex with PS1. Over expression of adoplin enhanced Aβ production.
3.By using the yeast two-hybrid system, we identified a novel Aβ-binding protein, AB-DIP, which contained CARD and nuclear targeting sequence. Overe-xpression of AB-DIP itself induced cell death and enhanced Aβ- induced cell death.
4.Neprilysin-knock-out mice were crossed with mutant PS1-transgenic mice. The mice did not show an enhancing effect of the Alzheimer phenotype.
|
