Small static electric field strength promotes aggregation-prone structures in amyloid-β(29-42)

J Chem Phys. 2017 Apr 14;146(14):145101. doi: 10.1063/1.4979866.

Abstract

The formation of senile plaques in central neural system resulting from the aggregation of the amyloid β (Aβ) of 40 and 42 residues is one of the two hallmarks of Alzheimer's disease. Numerous experiments and computational studies have shown that the aggregation of Aβ peptides in vitro is very complex and depends on many factors such as pH, agitation, temperature, and peptide concentration. The impact of a static electric field (EF) on amyloid peptide aggregation has been much less studied, although EFs may have some applications to treat Parkinson's disease symptoms. Here, we study the influence of an EF strength of 20 mV/nm, present in the human brains, on the conformation of the Aβ29-42 dimer. Our 7 μs non-equilibrium atomistic simulations in aqueous solution show that this field-strength promotes substantially the formation of β-hairpins, believed to be a very important intermediate state during aggregation. This work also suggests that structural biology experiments conducted under appropriate EF strengths may help reduce the conformational heterogeneity of Aβ1-40/Aβ1-42 dimers and provide significant insights into their structures that may be disease-causing.

MeSH terms

  • Amino Acid Sequence
  • Amyloid / chemistry
  • Amyloid / metabolism
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Brain / metabolism
  • Brain / physiology
  • Humans
  • Molecular Dynamics Simulation
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Protein Aggregation, Pathological
  • Protein Multimerization
  • Protein Structure, Secondary
  • Static Electricity

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Peptide Fragments
  • beta-amyloid peptide (29-42)