The inhibition of gamma-secretase as a therapeutic approach to Alzheimer's disease

Drug News Perspect. 2004 Jun;17(5):321-5. doi: 10.1358/dnp.2004.17.5.829036.

Abstract

Alzheimer's disease is a dementing neurodegenerative disorder for which there is no effective treatment at present. Genetic and biological studies provide evidence that the production and deposition of amyloid-beta peptides (Abeta contribute to the etiology of Alzheimer's disease. gamma-Secretase is the pivotal enzyme in generating the C terminus of Abeta which determines its aggregability and speed of deposition. Drugs that regulate the production of Abeta by inhibiting gamma-secretase activity could provide an effective therapy for Alzheimer's disease, although recent studies suggest that gamma-secretase plays important roles in cellular signaling. This review focuses on studies of the gamma-secretase biology and provides the direction for developing effective and selective gamma-secretase inhibitors as drugs for the treatment of Alzheimer's disease.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / pathology
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Aspartic Acid Endopeptidases
  • Endopeptidases / metabolism*
  • Humans
  • Membrane Proteins / metabolism
  • Presenilin-1
  • Presenilin-2
  • Protease Inhibitors / pharmacology*
  • Protease Inhibitors / therapeutic use

Substances

  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2
  • Protease Inhibitors
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human