Proteolysis of A beta 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 A beta sequence of amino acid residues 10-20. Our aim was to test if this enzyme could also degrade the insoluble 40-42 residues long A beta peptides purified from Alzheimer Disease brain. Our results indicate that MMP2 hydrolyzes A beta 1-40 and A beta 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 A beta 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 A beta 1-40(42).