Sulfated glycosaminoglycans in protein aggregation diseases

Protein aggregation diseases are characterized by intracellular or extracellular deposition of misfolded and aggregated proteins. These aggregated deposits contain multiple proteinaceous and non-protein components that are thought to play critical roles in the etiology and pathogenesis of protein aggregation diseases in vivo. One of these components, the sulfated glycosaminoglycans (GAGs), includes heparan sulfate, chondroitin sulfate, and keratan sulfate. The sulfated GAGs are negatively charged heteropolysaccharides expressed in all mammalian tissues. Enzymatically generated structural patterns and the degree of sulfation in GAGs determine GAGs' specific interactions with their protein ligands. Here, we review the potential roles of the sulfated GAGs in the pathogenesis and progression of protein aggregation diseases from a perspective of their sulfation modification. We also discuss the possibility of sulfated GAGs as therapeutic targets for protein aggregation diseases.