Proteolysis of Aβ Peptide from Alzheimer Disease Brain by Gelatinase A

It has been recently reported that the 72 kDa proteolytic enzyme gelatinase A/type IV collagenase/matrix metalloproteinase 2 (MMP2) hydrolyzed the Lys 16-Leu 17 peptide bond of a synthetic decapeptide (YEVHHQKLVFF) representing the soluble Aβ sequence of amino acid residues 10-20. Our aim was to test if this enzyme could also degrade the insoluble 40-42 residues long Aβ peptides purified from Alzheimer Disease brain. Our results indicate that MMP2 hydrolyzes Aβ_1-40 and Aβ_1-42 peptides at Lys 16-Leu 17, at Leu 34-Met 35, and Met 35-Val 36 peptide bonds. These results suggest that MMP2 has the ability of degrading Aβ of AD in vitro. If this hydrolysis also occurs in the brain′s extracellular matrix, the enzymatic action of gelatinase A could prevent the generation of amyloidogenic Aβ_1-40(42).