One of the most significant challenges to human society represents the emergence of neurodegenerative diseases in industrialized countries. The problems associated with these unmet medical needs are accentuated by so-far limited treatments and the continuing increase in life expectancy. The economic and social impact on patients and their families is considered severe. Many of the neurodegenerative diseases are associated with a decrease of neurites over time. Therefore, one successful therapeutic option represents the stimulation of neurite outgrowth. An appealing strategy involves the use of small molecule natural products, derived from plant or bacterial sources. In this project, we propose to prepare such neuronal growth factors derived from natural products in order to understand, control and direct neurite outgrowth. Natural product total synthesis will provide the neurite growth factors and their action on neurite outgrowth will be biologically evaluated. Structure activity relationships help to delineate the mode of action and facilitate the discovery of simpler analogs. A second part will be directed towards the molecular understanding of the biological mode of action. Target identification will be carried out in order to characterize the responsble pathways. The proposed work combines our strong expertise in total synthesis, in neuroactive natural products, and in surface functionalization and thus enables exciting discoveries in neurobiology. This approach not only delivers potential small molecule drugs to treat neurodegenerative diseases but also provides unique tools to study and to direct neurite outgrowth helping to understand these fascinating biological phenomena.