Amyloid fibrils and associated hypersulfated glycosaminoglycans

Amyloid fibrils are insoluble protein aggregates characterized by a cross-beta sheet structure that accumulate in tissues during various amyloid diseases [1]. These fibrils are consistently associated with hypersulfated glycosaminoglycans (GAGs), which are long, negatively charged polysaccharides like heparan sulfate [1]. GAGs act as essential scaffolds that promote the misfolding of precursor proteins and stabilize the resulting fibrils against proteolytic degradation [1]. The interaction between the cationic regions of amyloid proteins and the anionic sulfate groups of GAGs is a key driver of amyloidogenesis [2]. This complex is a significant therapeutic target, with drugs like eprodisate designed to competitively inhibit GAG-amyloid interactions [2]. Furthermore, the high density of hypersulfated GAGs in amyloid deposits allows for the development of specific imaging agents and radiopharmaceuticals like the p5+14 peptide [3]. Targeting this interaction aims to prevent the growth of deposits and enhance the clearance of existing amyloid from organs [2]. Consequently, the amyloid-GAG complex represents a critical focal point for both the diagnosis and treatment of systemic and localized amyloidosis [3].

Other names

Amyloid-GAG complexAmyloid-associated glycosaminoglycansProteoglycan-amyloid depositsAmyloid-associated proteoglycans

Competitive inhibition of glycosaminoglycan binding to amyloidogenic proteins to prevent fibril formation and stabilization, or direct binding to the complex for diagnostic imaging and targeted therapy [2, 3].