Dye-binding assays for evaluation of the effects of small molecule inhibitors on amyloid (aβ) self-assembly

ACS Chem Neurosci. 2012 Nov 21;3(11):807-19. doi: 10.1021/cn300076x. Epub 2012 Aug 6.

Abstract

Dye-binding assays, such as those utilizing Congo red and thioflavin T, are among the most widely used tools to probe the aggregation of amyloidogenic biomolecules and for the evaluation of small molecule inhibitors of amyloid aggregation and fibrillization. A number of recent reports have indicated that these dye-binding assays could be prone to false positive effects when assessing inhibitors' potential toward Aβ peptides, species involved in Alzheimer's disease. Specifically, this review focuses on the application of thioflavin T for determining the efficiency of small molecule inhibitors of Aβ aggregation and addresses potential reasons that might be associated with the false positive effects in an effort to increase reliability of dye-binding assays.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / pharmacokinetics*
  • Benzothiazoles
  • Coloring Agents / pharmacokinetics
  • Congo Red / pharmacokinetics
  • Drug Discovery / methods*
  • False Positive Reactions
  • Fluorescent Dyes / pharmacokinetics*
  • Humans
  • Reproducibility of Results
  • Thiazoles / pharmacokinetics*

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Coloring Agents
  • Fluorescent Dyes
  • Thiazoles
  • thioflavin T
  • Congo Red