Transthyretin amyloid fibril (TTR amyloid fibril)

Transthyretin amyloid fibril refers to highly ordered, elongated protein aggregates generated from misfolded transthyretin (TTR) molecules. Under pathological conditions, the native TTR tetramer dissociates and unfolds; these monomeric intermediates self-assemble into fibrils composed of cross-β-sheet structures, characteristic of amyloid. These fibrils deposit systemically in tissues, disrupting cellular function and causing diseases such as familial amyloid polyneuropathy and cardiac amyloidosis. Clinical pathology varies by mutation and tissue environment, but fibril structure is largely consistent across most TTR variants. Therapies attempt to stabilize the native TTR tetramer or reduce TTR synthesis, thus preventing fibril formation and progression of amyloid diseases. Physiologically, misfolded TTR and its amyloid fibrils serve no normal function but contribute to chronic organ damage and degeneration.

Other names

Misfolded transthyretinTTR amyloidATTR amyloid fibrilTransthyretin-derived amyloid fibril

Stabilization of native TTR tetramer to prevent dissociation and aggregation (e.g., tafamidis, diflunisal, thyroxine); Decreased synthesis of TTR (e.g., patisiran, inotersen); Inhibition of amyloid fibril formation by small molecules