Gelatinase A possesses a beta-secretase-like activity in cleaving the amyloid protein precursor of Alzheimer's disease.

The ability of the 72 kDa gelatinase A to cleave the amyloid protein precursor (APP) was investigated. HeLa cells were transfected with an APP695 plasmid. The cells were incubated with gelatinase A, which cleaved the 110 kDa cell-surface APP, releasing a 100 kDa form of the protein. A peptide homologous to the beta-secretase site was cleaved by gelatinase A adjacent to a glutamate residue at position -3 (beta A4 numbering system). A peptide homologous to the alpha-secretase site was not cleaved. The results demonstrate that 72 kDa gelatinase A is not an alpha-secretase, but that it may have a beta-secretase activity.