Gelatinase A possesses a β‐secretase‐like activity in cleaving the amyloid protein precursor of Alzheimer's disease

Abstract

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 β‐secretase site was cleaved by gelatinase A adjacent to a glutamate residue at position −3 (βA4 numbering system). A peptide homologous to the α‐secretase site was not cleaved. The results demonstrate that 72 kDa gelatinase A is not an α‐secretase, but that it may have a β‐secretase activity.