Role of Fucosyl Saccharides in Neuronal Communication

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DESCRIPTION (provided by applicant): This project seeks to understand the molecular mechanisms by which fucosyl saccharides influence recognition and communication between nerve cells in the brain. Several lines of evidence suggest that fucose alpha (1-2) galactose (Fuc alpha(1-2)Gal) saccharides play an important role in modulating neuronal connections important for long-term memory. Relatively little is known, however, about their precise structures or function in the brain. The proposed research combines chemistry and neurobiology to identify the molecular components - i.e., fucosyl saccharides, glycoproteins and lectins - and to study the mechanisms by which they regulate the flow of information across the synapse. The specific aims of this project are to: 1. Identify Fuc alpha(1-2)Gal lectins in the brain 2. Identify Fuc alpha(1-2)Gal glycoproteins in the brain 3. Investigate whether the Fuc alpha(1-2)Gal functions as a "recognition element" by examining pair wise interactions between identified lectins and glycoproteins and by studying their contribution to neuronal morphology and synaptic transmission 4. Investigate whether the Fuc alpha(1-2)Gal epitope functions as a "targeting element" to regulate the trafficking of glycoproteins to the synapse The long-term goal of this program is to provide a better understanding of the molecular and cellular basis of nerve cell communications and, ultimately, long-term memory formation. Because the program takes a distinctly chemical approach, these studies may ultimately reveal novel points of therapeutic intervention and enable the design of molecules capable of modulating cognition and improving deficits associated with age and neurodegenerative disease.