CATHEPSIN-B GENERATES THE MOST COMMON FORM OF AMYLOID-A (76 RESIDUES) AS A DEGRADATION PRODUCT FROM SERUM AMYLOID-A

Amyloid A protein (AA), the chief constituent of reactive amyloid deposits, is derived from serum amyloid A (SAA) and most commonly corresponds to the amino-terminal 76 residues (AA76). Digestion of recombinant human SAA1 with a lysosomal thiol protease, cathepsin B, and analysis of the products by SDS-PAGE and amino-terminal sequencing revealed that AA76 was generated as a minor and transient degradation product. Digestion with neutrophil elastase generated intermediates different from AA76. This finding suggests that cathepsin B may play an important role in amyloid fibrilogenesis by converting SAA to AA.