Date of Award
Chondroitin sulfate proteoglycans (CSPGs) and keratan sulfate proteoglycans (KSPGs) play an important role in neural development. Aggrecan, a CSPG, operates in the neural extracellular matrix where it negatively regulates neurite outgrowth to prevent aberrant process formation. Unfortunately, this aggrecan or CSPG-rich/KSPG-rich barrier can also prevent neuronal regeneration, which contributes to the inability to repair brain and spinal cord injuries. Removal of CSPGs and KSPGs has been shown to increase neurite outgrowth. We extend these findings by testing the ability of structurally-defined glycans to outcompete aggrecan and allow neurite outgrowth. Our overall goal is to determine if there is a particular glycan structure which can overcome inhibitory CSPGs and KSPGs without inhibiting neurite outgrowth themselves. We utilized primary cultures of rat neurons and applied polydisperse-related mixtures of CSPGs, KSPGs and newly-isolated, novel glycans in the absence and presence of aggrecan. Several of these glycans successfully removed the aggrecan-induced blockade while not inhibiting neurite outgrowth on their own. We are currently investigating the efficacy of these compounds in concentration-response curves and are testing additional glycans with different molecular weights and varying sulfation patterns to determine the structural requirements for the glycans as modulators of neurite outgrowth. By investigating the impacts of these glycans, we will increase the understanding of proteoglycan regulation of neural structure and function, and potentially identify compounds which could be used to treat spinal cord injuries.
Hartman, Gabriella D., "Regulating Neuronal Growth with Structurally Defined Glycans" (2020). Honors Theses. 1430.
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