Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of...

Glycosaminoglycans (GAGs) are a diverse family of ancient biomolecules that evolved over millennia as key components in the glycocalyx that surrounds all cells. GAGs have molecular recognition and cell instructive properties when attached to cell surface and extracellular matrix (ECM) proteoglycans (PGs), which act as effector molecules that regulate cellular behavior. The perception of mechanical cues which arise from perturbations in the ECM microenvironment allow the cell to undertake appropriate biosynthetic responses to maintain ECM composition and tissue function. ECM PGs substituted with GAGs provide structural support to weight-bearing tissues and an ability to withstand shear forces in some tissue contexts. This review outlines the structural complexity of GAGs and the diverse functional properties they convey to cellular and ECM PGs. PGs have important roles in cartilaginous weight-bearing tissues and fibrocartilages subject to tension and high shear forces and also have important roles in vascular and neural tissues. Specific PGs have roles in synaptic stabilization and convey specificity and plasticity in the regulation of neurophysiological responses in the CNS/PNS that control tissue function. A better understanding of GAG instructional roles over cellular behavior may be insightful for the development of GAG-based biotherapeutics designed to treat tissue dysfunction in disease processes and in novel tissue repair strategies following trauma. GAGs have a significant level of sophistication over the control of cellular behavior in many tissue contexts, which needs to be fully deciphered in order to achieve a useful therapeutic product. GAG biotherapeutics offers exciting opportunities in the modern glycomics arena.