Amyloid-β/Drug Interactions from Computer Simulations and Cell-Based Assays

J Alzheimers Dis. 2018;64(s1):S659-S672. doi: 10.3233/JAD-179902.

Abstract

Targeting the early oligomers formed by the amyloid-β (Aβ) peptide of 40 and 42 amino acids is considered one promising therapeutic approach for Alzheimer's disease (AD). In vitro experiments and computer simulations are often used in synergy to reveal the modes of interactions of drugs. In this account, we present our contribution to understanding how small molecules bind to Aβ40/Aβ42 peptides, based either on extensive coarse-grained and all-atom simulations, or a variety of experimental techniques. We conclude by offering several perspectives on the future of this field to design more efficient drugs.

Keywords: Alzheimer’s disease; Aβ oligomers; all-atom/coarse-grained models; amyloid simulations; cell-based assays; drugs; in vitro studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Cell Line, Tumor
  • Computer Simulation*
  • Drug Design
  • Humans
  • Models, Molecular*
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Protein Conformation
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)