IN-VITRO DEGRADATION OF SERUM AMYLOID-A BY CATHEPSIN-D AND OTHER ACIDPROTEASES - POSSIBLE PROTECTION AGAINST AMYLOID FIBRIL FORMATION

The effects of acid proteases on degradation of serum amyloid A protei n (SAA) were investigated in vitro. Human recombinant SAA1 (rSAA1), wh en incubated with human spleen extracts at pH 3.2, was degraded in the amino-terminal portion of the molecule. This reaction was inhibited b y an acid protease inhibitor, pepstatin. The degraded SAA molecules la cking nine or more amino-terminal residues, when exposed to in vitro f ibril-forming conditions, failed to form Congo red positive precipitat es and did not show amyloid fibril-like structure by electron microsco py. This suggests that the amino-terminal portion of SAA is essential for fibril formation. Cathepsin D, one of the lysosomal enzymes, also initiated degradation of rSAA1 at the amino-terminus. Cathepsin D immu noreactivity was detected in marginal areas of amyloid deposits in spl eens from patients with reactive amyloidosis. These findings suggest t hat cathepsin D or similar acid proteases may be involved in SAA catab olism and may protect against amyloid formation.