Modulation of Neuronal Differentiation by Growth Factor-Like Phospholipids

IBN-9722969 加博尔·蒂吉 这项研究的目的是了解调节大脑神经元连接发育的基本机制。 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），它们抑制了提供神经系统布线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，并且可能在脊髓损伤、中风和脑出血等事件后损害其再生和功能恢复。 未来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，我们将产生，使用分子生物学技术，特殊的细胞系，是缺乏三个关键的分子开关，Cdc 42，Rac，和Rho，这可能是参与抑制作用。 通过使用这些工程化的神经元样细胞，我们将能够回答这三个开关中的哪一个需要被打开以使抑制发生。 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，因此可能导致新的治疗方法，可以预防中枢神经系统缺乏再生的患者瘫痪。

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.