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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Alzheimer's disease;Amyloid;Gelatinase;Secretase;Protease;βA4;amyloid protein;AD;Alzheimer's disease;APP;amyloid protein precursor;APMA;4-aminophenylmercuric acetate