ANS binding reveals common features of cytotoxic amyloid species

ACS Chem Biol. 2010 Aug 20;5(8):735-40. doi: 10.1021/cb1001203.


Oligomeric assemblies formed from a variety of disease-associated peptides and proteins have been strongly associated with toxicity in many neurodegenerative conditions, such as Alzheimer's disease. The precise nature of the toxic agents, however, remains still to be established. We show that prefibrillar aggregates of E22G (arctic) variant of the Abeta(1-42) peptide bind strongly to 1-anilinonaphthalene 8-sulfonate and that changes in this property correlate significantly with changes in its cytotoxicity. Moreover, we show that this phenomenon is common to other amyloid systems, such as wild-type Abeta(1-42), the I59T variant of human lysozyme and an SH3 domain. These findings are consistent with a model in which the exposure of hydrophobic surfaces as a result of the aggregation of misfolded species is a crucial and common feature of these pathogenic species.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / genetics
  • Anilino Naphthalenesulfonates
  • Cell Line
  • Fluorescence
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Muramidase / chemistry
  • Muramidase / metabolism
  • Mutation
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Protein Folding
  • Protein Structure, Secondary


  • Amyloid
  • Amyloid beta-Peptides
  • Anilino Naphthalenesulfonates
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • 1-anilino-8-naphthalenesulfonate
  • Muramidase