Chemical approaches to elucidating the neurobiology of carbohydrates

The field of chem. neurobiol. is rapidly evolving and providing insights into the mols. and interactions involved in brain development, neuronal communication and memory storage. We will describe the synergistic application of org. chem. and neurobiol. 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 chem. synthesize oligosaccharides, we demonstrate that a specific sugar epitope on CSPGs potently inhibits axonal growth. Blockage of the epitope 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 physiol. processes.