FORNEUROCELL

BAVARIAN RESEARCH NETWORK FOR ADULT NEURAL STEM CELLS

Identification of signalling pathways in the induction, differentiation and conservation of dopaminergic neurons in the embryonal and adult mid-brain

Different from other cells, stem cells demonstrate an unlimited self-renewal capacity and can be differentiated into a multitude of cell types. These outstanding properties facilitate the use of stem cells for transplantation therapy of many neurodegenerative diseases. Morbus Parkinson is characterized by the degeneration of nigrostriatal dopaminergic neurons. Transplantation of human foetal midbrain tissue - enriched with dopaminergic nerve cells - into the striatum, the projection area of degenerating dopaminergic neurons, induces symptomatic improvement of disease patterns. The application of embryonic stem cells for transplantation is similarly promising. However, limited availability, potential danger of tumour induction as well as possible immune reactivity represent currently unsolved problems for application of embryonic stem cells and foetal tissues. Activation of endogenous adult stem cells would overcome these difficulties. Within the brain, endogenous adult neural stem cells reside in the olfactory bulb and the hippocampus. Within the substantia nigra (SN) slowly proliferating cells that exhibit neurogenic potential can also be found. Aim of this project is to identify signal transduction cascades and their receptors, through which these endogenous cells in the SN can be activated and differentiated into dopaminergic neurons. The identification of appropriate receptors in animal models is decisive for the development of novel therapeutic approaches for the treatment of Morbus Parkinson. Thus, by biochemical reconstruction of therapeutical “small molecules”, aiming at the activation of these pathways, endogenous stem cell population could be stimulated to produce de novo dopaminergic neurons in vivo.