Role of the carboxy groups of triterpenoids in their inhibition of the nucleation of amyloid β42 required for forming toxic oligomers

Chem Commun (Camb). 2018 Jun 14;54(49):6272-6275. doi: 10.1039/c8cc03230k.

Abstract

Herein we report that a preferable inhibition of the nucleation phase of Aβ42, related to the formation of toxic oligomers, by triterpenoids from medicinal herbs originates from a salt bridge of their carboxy groups with Lys16 and 28 in Aβ42. Such a direct interaction targeting the monomer, dimer, and trimer suppressed further oligomerization. In contrast, the corresponding congeners without carboxy groups failed to do so.

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Anthraquinones / chemistry
  • Anthraquinones / pharmacology
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology*
  • Cell Line, Tumor
  • Humans
  • Lysine / chemistry
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology*
  • Pentacyclic Triterpenes / chemistry
  • Pentacyclic Triterpenes / pharmacology
  • Peptide Fragments / chemistry*
  • Protein Multimerization
  • Triterpenes / chemistry
  • Triterpenes / pharmacology

Substances

  • Amyloid beta-Peptides
  • Anthraquinones
  • Carboxylic Acids
  • Neuroprotective Agents
  • Pentacyclic Triterpenes
  • Peptide Fragments
  • Triterpenes
  • amyloid beta-protein (1-42)
  • uncarinic acid-C
  • Oleanolic Acid
  • asiatic acid
  • Lysine
  • rhein