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.
