title: Proteolysis of A beta peptide from Alzheimer disease brain by gelatinase A.
abstract: 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).
authors: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
authors: A E
authors: AE
authors: Roher
authors: T C
authors: TC
authors: Kasunic
authors: A S
authors: AS
authors: Woods
authors: R J
authors: RJ
authors: Cotter
authors: M J
authors: MJ
authors: Ball
authors: R
authors: R
authors: Fridman
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2