GELATINASE-A POSSESSES A BETA-SECRETASE-LIKE ACTIVITY IN CLEAVING THEAMYLOID PROTEIN-PRECURSOR OF ALZHEIMERS-DISEASE

The ability of the 72 kDa gelatinase A to cleave the amyloid protein p recursor (APP) was investigated, HeLa cells were transfected with an A PP(695) plasmid. The cells were incubated with gelatinase A, which cle aved the 110 kDa cell-surface APP, releasing a 100 kDa form of the pro tein. A peptide homologous to the beta-secretase site was cleaved by g elatinase A adjacent to a glutamate residue at position -3 (beta A4 nu mbering system), A peptide homologous to the alpha-secretase site was not cleaved. The results demonstrate that 72 kDa gelatinase A is not a n alpha-secretase, but that it may have a beta-secretase activity.