Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, heparan sulfate, keratan sulfate, and hyaluronan are key molecules that regulate various biological functions such as cell signaling, tissue development as well as regeneration, and construction of the extracellular matrix, viral infection mediated by interactions with growth factors, morphogens, and extracellular matrix components. GAGs, which are essential side chains of proteoglycans, are widely distributed throughout the extracellular matrix as well as on the cell surface. The diverse functions of GAGs are governed by their sulfation as well as epimerization modifications, which determine the specific and various binding properties with spatiotemporal regulations in the distinct organism, tissue, and cell type. Recent functional studies on GAGs demonstrated using knockout mice, mutant flies, nematodes, and zebrafish etc. Furthermore, the deficiency of GAGs was associated with a variety of human genetic disorders, including immunodeficiency, heart defects, neurological abnormalities, connective tissue diseases, and corneal dystrophy.

Recent functional studies on GAGs using knockout mice, mutant flies, nematodes, zebrafish, and human heritable diseases reveal the indispensable roles in diverse biological processes. Furthermore, the anabolism including sulfation as well as epimerization modifications and catabolism of GAGs spatiotemporally regulate the distinct functions. Owing to the fact that the fine structures including sulfation pattern and epimerization are very complex, the development of new therapeutics of GAGs is an area of great current interest and challenging. Heparin oligosaccharide is utilized worldwide as an anticoagulant. Furthermore, chondroitin sulfate and hyaluronan are also used in the treatment of dry eye disease. Therefore, oligosaccharides of GAGs and their mimetics might have the potential to be therapeutic agents for a variety of diseases such as cancers, viral infections, and neurodegenerative and connective disorders. Nevertheless, a comprehensive understanding of the functions of GAG and development of future medicines and treatments for GAG-related pathological process remains insufficient. Thus, we wish to achieve goals: to understand “homeostasis of GAGs, GAGstasis”, which is a process that controls quantity, quality and localization of GAGs and their modification, contributing to health and disease progression; and to provide the insight into potential new drugs, medicines, and diagnosis for human diseases caused by metabolic abnormality of GAGs.

In this Research Topic, we aim to provide evidence of current studies for understanding of GAGstasis and development of future potential drugs for GAG-related disorders. Therefore, this Research Topic is to collect original research articles, short communications, reviews, mini-reviews, methods/protocols, and perspectives.

• Metabolism of GAGs
• Chemical biology of GAGs
• GAG oligosaccharides
• GAGs as drugs
• Human genetic diseases in GAGs
• Nematode (C. elegans), fruit fly (D. melanogaster), and zebrafish (D. rerio) of GAGs
• Stem cells, iPS cells, and regenerative models
• Neuronal development of GAGs
• Tumor biology of GAGs
• Pathobiochemistry of GAGs
• Regulations of proteoglycans by GAGs
• Interactions of GAGs with various proteins

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Glycosaminoglycan Homeostasis (“GAGstasis”): Mechanisms, Disruption in Disease, and Emerging Therapeutic Strategies