| Project/Area Number |
17590196
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General physiology
|
|---|
| Research Institution | National Cardiovascular Center Research Institute |
|---|
Principal Investigator |
NISHITANI Tomoe National Cardiovascular Center Research Institute, Dept.of Molecular Physiology, Laboratory chief, 循環分子生理部, 室長 (50393244)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Ca^<2+>-binding protein / Survival / Excitable cells |
|---|
| Research Abstract |
Molecular basis of survival from neuronal injury is essential for development of therapeutic strategy to remedy neurodegenerative disorders. Here, we demonstrate that neuronal Ca^<2+>-sensor 1 (NCS-1) ; one of key proteins for various neuronal functions also acts as an important neuronal survival factor. Overexpression of NCS-1 rendered cultured neurons more tolerant to cell death caused by several kinds of stressors ; while the dominant-negative mutant (E120Q) accelerated it. In addition, NCS-1 proteins increased upon treatment with glial cell line-derived neurotrophic factor (GDNF) and mediated GDNF-survival signal in a Akt-dependent but MAPK-independent manner. Furthermore, NCS-1 is significantly up-regulated in response to axotomy-induced injury in the DMV neurons of adult rats in vivo and adenoviral overexpression of E120Q resulted in a significant loss of surviving neurons, suggesting that NCS-1 is involved in anti-apoptotic mechanism in adult motor neurons. Taken together, we propose that NCS-1 is a novel survival-promoting factor up-regulated in injured neurons, mediating the GDNF-survival signal via Akt pathway.
|
