Glycosaminoglycans and neuroprotection

Abstract

Glycosaminoglycans (GAGs) are basic building blocks of the ground substance of the extracellular matrix and present at the cellular level as an important component of the glycocalyx covering the cell membrane. In addition to the general role of GAGs in maintaining the integrity of the cell and extracellular matrix by retaining water, certain GAGs exhibit anticoagulant and neuroprotective properties and serve as cell-surface receptors for various molecules. Although heparin, a highly sulfated GAG, has been used as a drug for more than 70 years due to its anticoagulant attributes, the neuroprotective properties of GAGs came into focus only in recent years. The discovery of some of the roles GAGs play in the pathomechanism of numerous neurodegenerative disorders as well as shedding light on the neuroprotective properties of these compounds in animal studies raised the possibility that GAGs may provide an entirely new avenue in the treatment of neurodegenerative diseases. Indeed, some GAGs were successfully used to improve the cognitive function of patients with various neurodegenerative conditions (Ban et al. (1991, 1992); Conti et al. (1989a, b); Passeri and Cucinotta, (1989); Santini (1989). Although the mechanism by which the GAGs exhibit neuroprotective properties is not entirely clear, there is a general consensus that the major factors of the neuroprotective attributes of GAGs include the impact of GAGs on amyloidogenesis and the regulatory action of GAGs in the apoptotic pathway. © 2012 Springer-Verlag Berlin Heidelberg.