Replacement of lost dopaminergic neurons by neural transplantation with embryonic nigral tissue is a most promising approach to the treatment of Parkinson’s disease. However, the limited availability of human embryonic dopaminergic neurons makes the search for alternative sources of transplantable neurons a priority. Based on an existing collaboration, a French academic research group with expertise in neurobiology and brain disease and a German company specialized in cell isolation and molecular gene analyses united to investigate the regulation of dopaminergic diffentiation and to develop new tools for the purification of dopaminergic neurons.
We will analyze the molecular regulation of neuronal, in particular dopaminergic, diffentiation of new neurons that are permanently generated in the adult mammalian brain. To do so we will use sophisticated cell isolation strategies in concert with analysis of minute amounts of nucleic acids to observe changes in gene, transcript and protein expression in time and space. We will functionally test identified factors using in vivo assays and generate new tools for the isolation of neuronal subpopulations
We will improve already known and develop new approaches that allow the efficient and reliable purification of dopaminergic neurons at different points of maturation from cultured stem cells. Furthermore, we will use known and identify new surface markers of neural progenitor cells and pluripotent cells to generate positive and negative cell sorting methods that will lead to transplantable cells in the absence of contaminating pluripotent and proliferative cell types. We will demonstrate the efficiency of these positive and negative selection approaches via transplantation experiments in vivo.
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