Roher A E, Kasunic T C, Woods A S, Cotter R J, Ball M J, Fridman R
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
Biochem Biophys Res Commun. 1994 Dec 30;205(3):1755-61. doi: 10.1006/bbrc.1994.2872.
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).
最近有报道称，72 kDa的蛋白水解酶明胶酶A/IV型胶原酶/基质金属蛋白酶2（MMP2）可水解一种合成十肽（YEVHHQKLVFF）的赖氨酸16-亮氨酸17肽键，该十肽代表了氨基酸残基10-20的可溶性Aβ序列。我们的目的是测试这种酶是否也能降解从阿尔茨海默病大脑中纯化出的不溶性40-42个残基长的Aβ肽。我们的结果表明，MMP2在赖氨酸16-亮氨酸17、亮氨酸34-甲硫氨酸35以及甲硫氨酸35-缬氨酸36肽键处水解Aβ1-40和Aβ1-42肽。这些结果表明MMP2在体外具有降解阿尔茨海默病Aβ的能力。如果这种水解也发生在大脑的细胞外基质中，明胶酶A的酶促作用可能会阻止淀粉样蛋白生成性Aβ1-40（42）的产生。
