Novel role of a Ca^<2+>-binding protein NCS-1 as a survival promoting factor

神经损伤后存活的分子基础对神经退行性疾病治疗策略的发展至关重要。在这里，我们证明神经元Ca^<2+>-传感器1 (NCS-1)；作为神经元各种功能的关键蛋白之一，它也是一个重要的神经元存活因子。NCS-1的过表达使培养的神经元更能耐受多种应激源引起的细胞死亡；而显性阴性突变体E120Q则加速了这一过程。此外，NCS-1蛋白在胶质细胞系来源的神经营养因子（GDNF）处理后增加，并以akt依赖但不依赖mapk的方式介导GDNF存活信号。此外，在体内成年大鼠的DMV神经元中，NCS-1在axocut诱导的损伤中显著上调，而腺病毒过表达E120Q导致存活神经元的显著损失，这表明NCS-1参与了成年运动神经元的抗凋亡机制。综上所述，我们认为NCS-1是一种新的存活促进因子，在损伤神经元中上调，通过Akt通路介导gdnf -存活信号。

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.