Amyloid fibril–heparan sulfate proteoglycan complex

Amyloid fibrils are insoluble, β-sheet-rich protein aggregates that accumulate in tissues and are characteristic of several neurodegenerative diseases, particularly Alzheimer’s disease. Heparan sulfate proteoglycans (HSPGs) are complex molecules consisting of one or more heparan sulfate glycosaminoglycan chains attached to a core protein, found abundantly in the extracellular matrix and on cell surfaces. HSPGs bind directly to amyloid fibrils, accelerating their formation, stabilizing aggregates, and promoting their persistence in tissues. This interaction supports the structural formation of amyloid plaques and contributes to their pathogenicity in neurodegenerative diseases by enhancing neurotoxicity, reducing plaque clearance, and promoting neuroinflammation. While interventions targeting this interaction have been proposed for therapeutic development, the molecular pair is not a discrete canonical target but a pathologically relevant interaction between two distinct molecular families.

Other names

Amyloid–HSPG complexAmyloid–heparan sulfate interactionsAmyloid plaques (when referencing aggregated Aβ fibrils with HSPG)

Inhibitors and mimetics can block or disrupt interaction between amyloid fibril and HSPG, slowing amyloid aggregation or deposition