Potential Therapeutic Application of Chondroitin Sulfate/Dermatan Sulfate

Shuhei      Yamada; Kazuyuki      Sugahara

doi:10.2174/157016308786733564

Abstract

Glycosaminoglycans (GAGs) are complex polysaccharides, which play important roles in cell growth, differentiation, morphogenesis, cell migration, and bacterial/viral infections. Major GAGs include heparin (Hep)/heparan sulfate, and chondroitin sulfate (CS)/dermatan sulfate (DS). Hep has been used for the treatment of thromboembolic disorders for more than 75 years, and has an established position in therapy today. CS/DS has attracted less attention and its clinical use is limited. However, CS/DS also have intriguing biological activities, which in turn should help in the development of CS/DS-based therapeutics. In this review, the following potential applications of CS/DS chains are discussed. (1) Sugar drugs for parasitic and viral infections. Particular CS variants appear to be involved in infections of various microbes, suggesting that CS/DS oligosaccharide sequences specifically interacting with microbes will lead to the development of inhibitory drugs for these infections. (2) Regenerative medicine. Biological activities of CS/DS chains possibly involve various growth factors, also known as Hep-binding growth factors. Specific CS/DS chains recruit growth/neurotrophic factors and/or potentiate their activities, suggesting that minute amounts of functional CS/DS chains can be utilized for tissue regeneration instead of signaling proteins. (3) Anti-tumor drugs. Specific saccharide structures in CS/DS chains appear to be involved in tumor cell proliferation and metastasis. The detection and identification of such CS/DS saccharide sequences would be an important contribution to cancer therapy.

Keywords: Glycosaminoglycan, chondroitin sulfate, dermatan sulfate, virus, infection, tissue regeneration, neurite outgrowth, osteoarthritis, cancer