Role of Nlrx1 in neuronal death

神经细胞死亡是在发育期间和整个成年期塑造中枢神经系统的一个基本过程。为了克服炎症或饥饿期间的细胞应激，神经元可以激活分子通路，将细胞能量重新定向，以实现最佳生存。或者，神经元可以激活导致细胞程序性死亡(或细胞自杀)的通路。我建议研究一种名为NLRX1的新蛋白质在细胞存活和细胞自杀机制中的作用。NLRX1是最近发现的调节植物和哺乳动物免疫反应的蛋白质家族的成员。以往的报道表明，NLRX1在抑制免疫反应中起着关键作用。我们的初步数据表明，NLRX1在神经元的死亡和存活中发挥作用。我们观察到，在没有NLRX1的情况下，显著更多的神经元死亡。利用当代细胞生物学的现代技术，我们将找到强调神经元动态平衡的关键特征。神经细胞死亡和存活的确切机制尚不清楚。加拿大科学界正在投入大量精力来了解神经元存活的分子基础。这项建议旨在研究一种新的蛋白质在细胞自杀的分子途径中的作用。这些研究的结果将有助于理解神经元如何在生死之间做出决定的机制。从拟议的工作中吸取的教训将促进我们对炎症期间如何维持中枢神经系统内稳的了解。

Neuronal cell death is a fundamental process that shapes the central nervous system during development and throughout adulthood. To overcome cellular stress during inflammation or starvation, neurons can activate molecular pathways that will redirect cellular energy for optimal survival. Alternatively, neurons can activate pathways, which lead to programmed cell death (or cellular suicide). I propose to study a role of the novel protein named Nlrx1 in mechanisms of cellular survival and cellular suicide. Nlrx1 is a member of recently discovered family of proteins, which regulate immune responses in plants and mammals. Previous reports suggest that Nlrx1 plays crucial role in suppressing immune response. Our preliminary data suggests that Nlrx1 plays a role in neuronal death and survival. We observed that a significantly larger number of neurons died in the absence of Nlrx1. Using modern techniques of contemporary cellular biology, we will find key features that underline neuronal homeostasis. The precise mechanism of neuronal cell death and survival is unknown. Canadian scientific community is putting a lot of effort to understand molecular basis of neuronal survival. This proposal is aimed to study role of a novel protein in the molecular pathway of the cellular suicide. The results of these studies will help to understand mechanisms of how neurons make a decision between life and death. The lesson learned from proposed work will advance our knowledge of how central nervous system homeostasis is maintained during inflammation.