A hybrid molecule that prohibits amyloid fibrils and alleviates neuronal toxicity induced by beta-amyloid (1-42)

Biochem Biophys Res Commun. 2005 Mar 25;328(4):816-23. doi: 10.1016/j.bbrc.2005.01.030.

Abstract

Inhibition of oligomeric amyloid beta (Abeta) peptide or fibril formation has emerged as a major therapeutic target for developing new drugs for Alzheimer's disease. We focused on developing inhibitors by synthesizing hybrid molecules of ferulic acid and styryl benzene, which has been known as a fibril binder. Initially, cell-based assay was carried out to evaluate the effective compound. A selected effector, 1, alleviated the Abeta-induced neuronal toxicity in differentiated SH-SY5Y human neuroblastoma cells. The effector could also inhibit Abeta fibril formation, monitored by thioflavin T fluorescence intensity assay and transmitted electron microscopic images. A strong binding affinity of 1 to non-fibrous monomer-like Abeta, which was immobilized to a surface chip, was measured using a surface plasmon resonance technique. The data suggest that the effector shifts the equilibrium of multimeric Abeta, inhibiting the pathogenic oligomer or fibril formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Benzene / chemistry
  • Benzene / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Coumaric Acids / chemistry
  • Coumaric Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Drug Interactions
  • Humans
  • Neuroblastoma / pathology*
  • Neurons / drug effects*
  • Neurons / pathology*
  • Peptide Fragments / toxicity*

Substances

  • Amyloid beta-Peptides
  • Coumaric Acids
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • ferulic acid
  • Benzene