1120 - 1200 Linda C Hsieh-Wilson

Chemical approaches to elucidating the neurobiology of carbohydrates 

The field of chemical neurobiology is rapidly evolving and providing insights into the molecules and interactions involved in brain development, neuronal communication and memory storage. We will describe the synergistic application of organic chemistry and neurobiology to understand how specific carbohydrate structures contribute to neuronal growth and regeneration. Chondroitin sulfate proteoglycans (CSPGs) represent a major barrier to regenerating axons in the central nervous system (CNS), but the structural diversity of the polysaccharides has hampered efforts to understand their activity. By taking advantage of our ability to chemically synthesize oligosaccharides, we demonstrate that a specific sugar epitope on CSPGs potently inhibits axonal growth. Blockage of the epitope using an antibody reversed CSPG-mediated growth inhibition and stimulated axon regeneration in vivo, suggesting a novel therapeutic approach to CNS repair. More broadly, our studies support the notion that specific sulfation sequences within chondroitin sulfate polysaccharides direct the activity of proteins in vivo and coordinate key physiological processes.