Molecular mechanisms of fibrin functions at the neurovascular interface

最近，脑血管系统的作用已经从营养物质的供应者扩展到在发育和成人神经发生过程中驱动轴突引导的血管生成生态位。识别负责神经血管通讯的新因素对于神经元存活和神经发生的分子理解是必要的。在宿主实验室的研究发现，纤维蛋白是一种血液来源的蛋白质，在神经血管稳态紊乱后沉积在神经系统中，作为神经元再生的抑制剂和中枢神经系统脱髓鞘的调节剂。纤维蛋白与大量受体相互作用，介导控制细胞存活、分化和活化的信号通路。尽管纤维蛋白作用所需的信号机制存在于神经细胞和神经功能介质（如小胶质细胞）中，但纤维蛋白在神经系统中的作用尚未被表征。本项目的中心目标是了解纤维蛋白信号在神经元存活和神经发生中的分子基础。该项目的研究将涉及细胞参与者的识别和表征，纤维蛋白使用最先进的体内和体外技术来调节其在神经系统中的作用，包括受体和信号机制。

The role of the brain vasculature has been recently extended from a supplier of nutrients to an angiogenic niche that drives axon guidance during development and adult neurogenesis. The identification of novel factors responsible for neurovascular communication is necessary for the molecular understanding of neuronal survival and neurogenesis. Studies at the host lab have identified fibrin, a blood-derived protein deposited in the nervous system after perturbations of the neurovascular homeostasis, as an inhibitor of neuronal regeneration and a regulator of demyelination in the CNS. Fibrin interacts with a plethora of receptors and mediates signaling pathways that control cell survival, differentiation and activation. Although the signaling machinery necessary for fibrin actions is present in both neuronal cells and mediators of neuronal functions, such as microglia cells, the effects of fibrin in the nervous system have not been characterized. The central goal of this project is to understandthe molecular basis of fibrin signaling on neuronal survival and neurogenesis. The studies in this project will involve the identification and characterization of the cellular players, the receptors and signaling mechanisms used by fibrin to mediate its effects in the nervous system using state-of-the-art in vivo and in vitro techniques.