Grant: Project Grant

Brain cell death following injuries or stresses often lead to permanent disabilities; this is largely due to the poor abilities of brain cells to re-grow. In contrast, the adult nerve cells of Lymnaea stagnalis, a freshwater pond snail, show a greater ability to survive and to spontaneously regenerate following injury. Thus, it is likely that the snail nerve cells carry the message essential for cell survival and for nerve regeneration. This message may be carried by novel proteins which are not found in mammals. This brings about one innovative approach to identify the novel invertebrate proteins that promote cell survival and nerve re-growth and test whether insertion of this novel protein into mammalian central neurons, such as mouse and human neurons, can rescue nerve cells from cell death. We have recently found a number of novel snail proteins that are required for nerve cell growth and regeneration following injury in snail. In this study, we characterize the effects of caltubin, one of these novel proteins, on property of mammalian neurons and investigate the cellular and molecular mechanisms of caltubin in cell survival and nerve re-growth of these cells. We hypothesized that caltubin regulates the stability of the nerves thus prevents cells from death after injury. We will identify specific regions of this protein that are responsible for the effects of caltubin in mouse brain cells, and create new small caltubin peptides to promote cell survival and reserve cell integrate following injury or stress conditions. We will use multiple advanced molecular, biochemical and optical imaging techniques in combination of cell culture and animal models in this study. We anticipate these experiments will assist us to develop new drugs for neuroprotection in the future. This study highlights the potential of an innovative strategy for developing new neuroprotective drugs against cell death in neurological diseases.