Amyloidogenic transthyretin fibril (ATTR fibril)

Amyloidogenic transthyretin (ATTR) fibrils are insoluble protein aggregates formed by the misfolding and polymerization of transthyretin (TTR) monomers. Transthyretin is a homotetrameric protein synthesized primarily in the liver and choroid plexus, responsible for transporting thyroxine and retinol-binding protein in the blood and cerebrospinal fluid (UniProt: P02766). In ATTR amyloidosis, the tetramer dissociates into monomers that undergo conformational changes to form amyloid fibrils, which deposit in the extracellular space of organs such as the heart and peripheral nerves (PubMed: 31216254). The fibril ends are critical kinetic sites where misfolded monomers are recruited and incorporated, driving the elongation and propagation of the amyloid mass. Therapeutic strategies targeting these fibrils include monoclonal antibodies like NI006 and PRX004, which are designed to bind specifically to misfolded or fibrillar TTR to promote clearance by macrophages and inhibit further growth (PubMed: 36516075, PubMed: 31871115). This approach directly addresses the existing pathological burden, complementing other therapies that stabilize the TTR tetramer or silence TTR gene expression.

Other names

Transthyretin amyloidATTR amyloidTTR fibrilMisfolded transthyretin aggregateAmyloidogenic transthyretin fibril ends

Inhibition of fibril elongation by capping growth sites (fibril ends) and promotion of antibody-mediated phagocytic clearance of existing amyloid deposits (PubMed: 36516075, PubMed: 23990617).