ABSTRACT
AA amyloidosis develops in patients with chronic inflammatory diseases. The AA amyloid protein is derived from serum amyloid A (SAA), an acute phase protein synthesized and mainly secreted by the liver, and lacks one or two amino acids at the N-terminus, and between 15 and 83 amino acids at the C-terminus. Macrophages are commonly found adjacent to amyloid deposits and are able to bind and internalize SAA, forming amyloid deposits in vitro. They synthesize a broad range of proteases, which may process the precursor protein, and may also be involved in the degradation of amyloid deposits. The endosomal and lysosomal compartments are particularly rich in cysteine proteases, such as cathepsin (Cath) B. Analysis of the degradation profile over time shows that CathB has mainly carboxypeptidase, some endoproteolytic and minor aminopeptidase activity. Degradation by CathB showed primarily carboxypeptidase activity. No degradation was observed in the absence of active protease or in the presence of E64.
