Amyloid fibrils and associated hypersulfated heparan sulfate proteoglycans (HSPG-amyloid complex)

Amyloid fibrils are insoluble protein aggregates characterized by a cross-beta sheet structure, which are a hallmark of various neurodegenerative and systemic diseases (Snow et al., 1987, Lab Invest). Hypersulfated heparan sulfate proteoglycans (HSPGs) are consistently found co-localized with these fibrils in vivo, where they play a critical role in the pathogenesis of amyloidosis (van Horssen et al., 2003, Lancet Neurol). HSPGs act as scaffolds that promote the misfolding of precursor proteins into fibrils and protect the resulting aggregates from proteolytic degradation, thereby facilitating their accumulation in tissues (Noborn et al., 2012, J Biol Chem). Targeting the interaction between amyloidogenic proteins and HSPGs represents a therapeutic strategy aimed at preventing fibril formation or enhancing their clearance. Drugs like eprodisate have been developed to competitively inhibit this binding, specifically in the context of AA amyloidosis (Dember et al., 2007, N Engl J Med). This complex is a key target for interventions seeking to disrupt the structural integrity and persistence of amyloid plaques across different disease states.

Other names

Amyloid-associated glycosaminoglycansHS-amyloid complexHeparan sulfate proteoglycans in amyloid depositsAmyloid-HSPG complex

Competitive inhibition of the binding between amyloidogenic precursor proteins and endogenous heparan sulfate proteoglycans to prevent fibril assembly, stabilization, and tissue deposition.