Anti-amyloidogenic activity of tetracyclines: studies in vitro

FEBS Lett. 2001 Jan 5;487(3):404-7. doi: 10.1016/s0014-5793(00)02380-2.

Abstract

Cerebral deposition of beta-amyloid is a major neuropathological feature in Alzheimer's disease. Here we show that tetracyclines, tetracycline and doxycycline, classical antibiotics, exhibit anti-amyloidogenic activity. This capacity was determined by the exposure of beta 1-42 amyloid peptide to the drugs followed by the electron microscopy examination of the amyloid fibrils spontaneously formed and quantified with thioflavine T binding assay. The drugs reduced also the resistance of beta 1-42 amyloid fibrils to trypsin digestion. Tetracyclines not only inhibited the beta-amyloid aggregates formation but also disassembled the pre-formed fibrils. The results indicate that drugs with a well-known clinical profile, including activity in the central nervous system, are potentially useful for Alzheimer's therapy.

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / drug effects*
  • Amyloid beta-Peptides / metabolism*
  • Benzothiazoles
  • Doxycycline / pharmacology
  • Fluorescent Dyes
  • Humans
  • Hydrolysis
  • In Vitro Techniques
  • Macromolecular Substances
  • Microscopy, Electron
  • Peptide Fragments / chemistry
  • Peptide Fragments / drug effects*
  • Peptide Fragments / metabolism*
  • Tetracycline / pharmacology
  • Tetracyclines / pharmacology*
  • Thiazoles
  • Trypsin / pharmacology

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Fluorescent Dyes
  • Macromolecular Substances
  • Peptide Fragments
  • Tetracyclines
  • Thiazoles
  • amyloid beta-protein (1-42)
  • thioflavin T
  • Trypsin
  • Tetracycline
  • Doxycycline