Speaker: Vimal Swarup. Advisor: Vladimir Hlady, Ph.D.

Abstract:

In the adult mammalian central nervous system (CNS), spontaneous repair following severe injury is incomplete and results in permanent neurological deficits in affected patients. This limited regenerative capacity of the CNS is attributed to inhibitory chondroitin sulfate proteoglycans (CSPGs), which are upregulated at the scar site. Conversely, a variety of CSPGs also interact with growth factors such as midkine and brain derived neurotropic factor (BDNF) to support neuronal growth, plasticity and regeneration. These multiple roles of CSPGs are mediated by diverse molecular sulfation patterns on their glycosaminoglycan (GAG) residues. A thorough understanding of the structure-function relationship of the CS-GAGs is of great biological and clinical interest. This study aims to decipher the effect of CSPG-GAGs and their sulfation on neuronal growth and design molecular strategies to suppress the inhibitory CSPGs produced in the CNS scar site. Insights obtained from this study will define the structural basis behind CS mediated neuronal growth and pathfinding, and will relate the molecular sulfation patterns of CS with their functional manifestations in the CNS.