In search of an enzyme: the beta-secretase of Alzheimer's disease is an aspartic proteinase

Trends Neurosci. 2000 Nov;23(11):565-70. doi: 10.1016/s0166-2236(00)01647-7.

Abstract

The deposition of beta-amyloid (Abeta) in the brain is a neuropathological feature of Alzheimer's disease. Abeta is cleaved from its precursor protein (APP) by processing at its N and C termini by enzymes known as beta- and gamma-secretases,respectively. The identity of these enzymes has been elusive but the search for the N-terminal secretase might have ended recently with the almost simultaneous publication by five major laboratories claiming a transmembrane aspartic proteinase to be the long sought after beta-secretase. Even at this early stage of its characterization, this aspartic proteinase fulfils many of the key criteria necessary for beta-secretase. The race is now on to develop inhibitors that could prove effective in halting the progression of Alzheimer's disease.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology*
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / antagonists & inhibitors
  • Aspartic Acid Endopeptidases / metabolism*
  • Brain / enzymology
  • Endopeptidases
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Protein Processing, Post-Translational
  • Tissue Distribution

Substances

  • Amyloid beta-Protein Precursor
  • Enzyme Inhibitors
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE2 protein, human
  • BACE1 protein, human