Translational Studied of Chondroitin Sulfate Proteoglycans

National Heart, Lung, And Blood Institute

Investigators

Linked publications, trials & patents

Abstract

The objective of this project is to develop potential approaches to the therapy of brain and spinal cord injury. One approach is to limit the production or increase the degradation of chondroitin sulfate proteoglycans (CSPGs). We have demonstrated that the enzyme arylsulfatase B (ARSB), which cleaves the 4-sulfate group from chondroitin sulfate only at the non-reducing end, can dramatically increase neuronal growth on substrates of chondroitin sulfate. We have investigated the role of CSPGS in the injured optic nerve following optic nerve crush. We have demonstrated a significant upregulation of CSPGs in the moue optic nerve. We have also shown that ARSB can significantly improve the regeneration of axons in the mouse optic nerve following optic nerve crush. A manuscript describing these results has been published. We published a thorough study of the distribution and changes in proteoglycan composition following optic nerve crush. This study identified that not all proteoglycans are likely to be involved in reducing regeneration after injury. We are now investigating the use of agents which promote axonal growth by altering neuronal intracellular signaling pathways in the optic nerve crush model. This manuscript has now been published.