Modulation of Neuronal Differentiation by Growth Factor-Like Phospholipids

Gabor Tigyi：这项研究的目的是了解调节大脑神经元连接发展的基本机制。这个小组过去的研究已经发现了一组新的分子（溶血磷脂酸盐），它们可以抑制提供神经系统线路的神经元过程的生长。有趣的是，这些分子是在中枢神经系统损伤后产生的，并可能在脊髓损伤、中风和脑出血等事件后损害中枢神经系统的再生和功能恢复。接下来6-12个月的工作将研究介导这种抑制作用的分子信号。具体来说，我们将利用分子生物学技术，生成缺乏Cdc42、Rac和Rho这三个关键分子开关之一的特殊细胞系，这些开关可能与抑制作用有关。通过使用这些工程神经元样细胞，我们将能够回答这三个开关中哪一个需要被打开才能发生抑制。一旦确定了介导抑制作用的开关，它们将成为药物开发的潜在目标，因此可能会导致新的治疗方法，可以防止因中枢神经系统缺乏再生而瘫痪的患者。

IBN-9722969 Gabor Tigyi The goal of this research is to understand the fundamental mechanisms that regulate the development of neuronal connections in the brain. Past research by this group has led to the discovery of a novel group of molecules (lysophosphatidates) that inhibit the outgrowth of neuronal processes that provide the wiring of the nervous system. Interestingly, these molecules are generated after injury to the central nervous system and might impair its regeneration and recovery of function after such events as spinal cord injury, stroke, and brain hemorrhage. The work proposed for the next 6-12 months will investigate the molecular signals that mediate this inhibitory effect. Specifically, we will generate, using molecular biological techniques, special cell lines that are deficient in one of three key molecular switches, Cdc42, Rac, and Rho, which are presumably involved in the inhibitory effect. By using these engineered neuron- like cells, we will be able to answer which of these three switches need(s) to be turned on for the inhibition to take place. Once the switches mediating the inhibitory effect are determined, they will become potential targets for drug development and therefore could lead to novel treatments that can prevent paralysis in patients suffering from lack of regeneration in the central nervous system.