2006 Fiscal Year Final Research Report Summary
Novel role of a Ca^<2+>-binding protein NCS-1 as a survival promoting factor
| Project/Area Number |
17590196
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | National Cardiovascular Center Research Institute |
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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)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Ca^<2+>-binding protein / Survival / Excitable cells |
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| 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.
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