• Tim Moderer, Ioana Puşcalău-Gîrţu, Christian Haupt, Julian Baur, Armando Rodríguez-Alfonso, Sebastian Wiese, Christoph Q Schmidt, Miroslav Malešević, Wolf-Georg Forssmann, Ludger Ständker, and Marcus Fändrich.
• Institute of Protein Biochemistry, Ulm University, Ulm, Germany.
• Amyloid. 2023 Dec 1; 30 (4): 424433424-433.

BackgroundSystemic AA amyloidosis is a world-wide occurring protein misfolding disease in humans and animals that arises from the formation of amyloid fibrils from serum amyloid A (SAA) protein and their deposition in multiple organs.ObjectiveTo identify new agents that prevent fibril formation from SAA protein and to determine their mode of action.Materials And MethodsWe used a cell model for the formation of amyloid deposits from SAA protein to screen a library of peptides and small proteins, which were purified from human hemofiltrate. To clarify the inhibitory mechanism the obtained inhibitors were characterised in cell-free fibril formation assays and other biochemical methods.ResultsWe identified lysozyme as an inhibitor of SAA fibril formation. Lysozyme antagonised fibril formation both in the cell model as well as in cell-free fibril formation assays. The protein binds SAA with a dissociation constant of 16.5 ± 0.6 µM, while the binding site on SAA is formed by segments of positively charged amino acids.ConclusionOur data imply that lysozyme acts in a chaperone-like fashion and prevents the aggregation of SAA protein through direct, physical interactions.

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