In vitro degradation of serum amyloid A by cathepsin D and other acid proteases: possible protection against amyloid fibril formation

Scand J Immunol. 1995 Jun;41(6):570-4. doi: 10.1111/j.1365-3083.1995.tb03609.x.


The effects of acid proteases on degradation of serum amyloid A protein (SAA) were investigated in vitro. Human recombinant SAA1 (rSAA1), when incubated with human spleen extracts at pH 3.2, was degraded in the amino-terminal portion of the molecule. This reaction was inhibited by an acid protease inhibitor, pepstatin. The degraded SAA molecules lacking nine or more amino-terminal residues, when exposed to in vitro fibril-forming conditions, failed to form Congo red positive precipitates and did not show amyloid fibril-like structure by electron microscopy. 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 immunoreactivity was detected in marginal areas of amyloid deposits in spleens from patients with reactive amyloidosis. These findings suggest that cathepsin D or similar acid proteases may be involved in SAA catabolism and may protect against amyloid formation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid / metabolism
  • Aspartic Acid Endopeptidases / metabolism*
  • Cathepsin D / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Kidney / enzymology
  • Liver / enzymology
  • Serum Amyloid A Protein / metabolism*
  • Spleen / enzymology


  • Amyloid
  • Serum Amyloid A Protein
  • Aspartic Acid Endopeptidases
  • Cathepsin D