beta-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies

Biochem Pharmacol. 2003 Feb 1;65(3):407-16. doi: 10.1016/s0006-2952(02)01514-9.

Abstract

The aggregation of beta-amyloid (1-40) (Abeta) induced by human recombinant acetylcholinesterase (HuAChE) was studied by means of circular dichroism (CD) and by thioflavin T fluorescence spectroscopy. Abeta was incubated alone and with HuAChE. The kinetic of fibrils formation was followed for 48 hr. The increasing beta-conformation content induced by HuAChE, preliminary to the formation of Abeta fibrils, was determined by circular dichroism. This phenomenon was found to be related to the thioflavin T emission of fluorescence at 490 nm. Incubation experiments were performed in the presence of known AChE inhibitors (physostigmine, edrophonium, decamethonium, propidium) and drugs used for Alzheimer's disease (AD) (tacrine, donepezil), to test their capability of preventing the HuAChE-induced Abeta aggregation. The non-competitive or mixed mode of AChE inhibition was confirmed to be an essential feature. At 100 microM propidium, decamethonium, donepezil and physostigmine were found to inhibit the HuAChE-induced Abeta aggregation by 82, 25, 22 and 30%, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / drug effects
  • Cholinesterase Inhibitors / pharmacology*
  • Circular Dichroism
  • Fluorometry
  • Humans
  • Peptide Fragments / biosynthesis*
  • Peptide Fragments / chemistry
  • Peptide Fragments / drug effects
  • Protein Conformation
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / pharmacology

Substances

  • Amyloid beta-Peptides
  • Cholinesterase Inhibitors
  • Peptide Fragments
  • Recombinant Proteins
  • amyloid beta-protein (1-40)
  • Acetylcholinesterase