Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics

The extracellular matrix (ECM) constitutes a highly dynamic 3D structural network comprised of proteoglycans (PGs) glycosaminoglycans (GAGs), collagens, laminins, fibronectin, elastin, other glycoproteins, and proteinases. In recent years, the field of PGs has expanded rapidly. The present review article summarizes major achievements and paradigm-shifting discoveries made on the PG/GAG chemistry-biology axis. Particular attention is given to the structural variability, structure-function relationships, metabolic, molecular, and epigenetic mechanisms underlying their synthesis. The article addresses recent insights related to exosome biogenesis, degradation, and cell signaling.

The status of these molecules as diagnostic tools and potential pharmacological targets in diseases, as well as current applications in nanotechnology and biotechnology, are also covered. Moreover, issues related to docking studies, molecular modeling, GAG/PG interaction networks, and their integration are discussed.