Mast cell proteases as modulators of the glial scar to promote neuroregeneration after trauma. (R-4208)

Axon regeneration after trauma in the mammalian adult central nervous system (CNS) is restricted due to numerous factors, such as the lack of growth-promoting factors, the low intrinsic capacity of neurons to survive from damage and, most importantly, the presence of growth-inhibitory factors. The most potent inhibitory components in the damaged CNS are molecules of the extracellular matrix (ECM), such as chondroitin sulphate proteoglycans (CSPGs). These proteoglycans become upregulated after injury by cells involved in the glial scarring process and they negatively influence neurite outgrowth in vitro and axon regeneration in vivo. In fact, breakdown of these CSPGs was found to improve functional outcome after CNS trauma. Until now, no efficacious factors are available that can efficiently modify the inhibitory ECM to promote regeneration and recovery after CNS injury. By focusing on molecules that can clear the path for axon growth, we will gain greater insight into the regulatory mechanisms underlying glial scarring, axon repair and functional recovery after injury. Both preliminary and published data from our research group indicated that mast cell proteases (MCPs) are key enzymes in neuroregenerative processes after CNS trauma. MCPs have the ability to digest ECM components and play important roles in wound healing and remodeling. It is, however, still not revealed if and how these proteases affect 'glial scarring', axon regeneration and functional recovery after CNS damage. Hence, we would like to unravel the role played by MCPs in the regulation of neuroregenerative processes after SCI. These results will further illuminate the basic mechanisms of glial inhibition and will uncover the potential of MCPs to improve clinical outcome after SCI.

Keywords:NEUROREGENERATION

Disciplines:Systems biology, Diagnostics, Laboratory medicine, Medicinal products