Do serine proteases degrade amyloid A fibrils?

Area of Science:

• Biochemistry
• Proteomics
• Enzymology

Background:

• Human serum possesses enzymes capable of degrading serum amyloid A protein (SAA) and amyloid A (AA) fibrils.
• Previous studies identified these enzymes as serine proteases, but detailed characterization is lacking.

Purpose of the Study:

• To investigate the specific serine proteases in human serum responsible for SAA and AA fibril degradation.
• To characterize the enzymatic activity on SAA and AA fibrils.

Main Methods:

• Incubation of SAA-containing serum with various serine proteases (chymotrypsin, trypsin, elastase, collagenase, kallikrein) at 37°C.
• Assessed SAA degradation into peptides.
• Evaluated the effect on Sirius-Red binding ability of amyloidotic tissue and isolated AA fibrils to determine conformational changes and degradation.

Main Results:

• Chymotrypsin, trypsin, elastase, collagenase, and kallikrein degraded SAA into peptides within 2 hours.
• All tested enzymes, except collagenase, destroyed the Sirius-Red binding ability of AA fibrils, indicating altered beta-pleated sheet conformation and potential degradation.
• Significantly higher enzyme concentrations were required to degrade amyloid fibrils compared to physiological serum levels.

Conclusions:

• Specific serine proteases in human serum can degrade SAA.
• While these serine proteases can alter or degrade AA fibrils in vitro, the high concentrations needed make them unlikely to be responsible for in vivo amyloid fibril degradation.
• Further research is needed to identify the in vivo mechanisms of AA fibril clearance.