Pan-amyloid fibrils

Pan-amyloid fibrils are insoluble, pathological protein aggregates characterized by a highly stable cross-beta sheet quaternary structure (Benson et al., 2018). These fibrils are formed by the misfolding of various precursor proteins—such as immunoglobulin light chains, transthyretin, or amyloid-beta—and are the hallmark of a group of disorders known as amyloidoses (Wall et al., 2022). In systemic amyloidosis, these deposits accumulate in the extracellular space of vital organs like the heart, kidneys, and liver, causing mechanical disruption and proteotoxicity that leads to progressive organ failure (Sanchorawala et al., 2023). Unlike therapies that target specific precursor proteins to prevent new fibril formation, pan-amyloid-targeted agents are designed to recognize the universal structural features or common associated components, such as Serum Amyloid P, common to all amyloid types (Attralus, 2024; Richards et al., 2015). This approach enables the development of "pan-amyloid" imaging agents for comprehensive disease staging and therapeutic antibodies or peptides that trigger the clearance of existing deposits by the immune system, potentially reversing organ damage across multiple disease subtypes (Wall et al., 2022).

Other names

Amyloid depositsMisfolded protein aggregatesCross-beta sheet fibrilsSystemic amyloid depositsAmyloid aggregates

Binding to the conserved cross-beta sheet structure of amyloid fibrils to enable diagnostic imaging or to recruit immune cells for fibril degradation and clearance.