muramidase and Immunoglobulin-Light-chain-Amyloidosis

Systemic 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.. To identify new agents that prevent fibril formation from SAA protein and to determine their mode of action.. We 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.. We 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.. Our data imply that lysozyme acts in a chaperone-like fashion and prevents the aggregation of SAA protein through direct, physical interactions.

Topics: Amyloid; Amyloidosis; Animals; Humans; Immunoglobulin Light-chain Amyloidosis; Muramidase; Serum Amyloid A Protein

Although the cure of amyloid related neurodegenerative diseases, non-neuropathic amyloidogenic diseases and non-neuropathic systemic amyloidosis are appealing energetic research attempts, beneficial medication is still to be discovered. There is a need to explore intensely stable therapeutic compounds, potent enough to restrict, disrupt or wipe out such toxic aggregates. We had performed a comprehensive biophysical, computational and cell based assay, that shows Nordihydroguaiaretic acid (NA) not only significantly inhibits heat induced hen egg white lysozyme (HEWL) fibrillation but also disaggregates preformed HEWL fibrils and reduces the cytoxicity of amyloid fibrils as well as disaggregated fibrillar species. The inhibitory potency of NA was determined by an IC

Topics: Amyloid; Amyloidosis; Benzothiazoles; Cell Line, Tumor; Hot Temperature; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Immunoglobulin Light-chain Amyloidosis; Inhibitory Concentration 50; Kinetics; Light; Masoprocol; Microscopy, Fluorescence; Molecular Docking Simulation; Muramidase; Nephelometry and Turbidimetry; Protein Aggregates; Protein Binding; Protein Conformation; Scattering, Radiation; Spectrometry, Fluorescence; Thiazoles