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

FEBS Lett. 1995 Dec 18;377(2):267-70. doi: 10.1016/0014-5793(95)01358-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans
  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Aspartic Acid Endopeptidases
  • Binding Sites
  • Endopeptidases / metabolism*
  • Extracellular Matrix Proteins*
  • Gelatinases / metabolism*
  • HeLa Cells
  • Humans
  • Lectins, C-Type
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / metabolism*
  • Molecular Sequence Data
  • Proteoglycans / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity


  • Aggrecans
  • Amyloid beta-Protein Precursor
  • Extracellular Matrix Proteins
  • Lectins, C-Type
  • Proteoglycans
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2