AβPP-selective BACE inhibitors (ASBI): novel class of therapeutic agents for alzheimer's disease

J Alzheimers Dis. 2013;37(2):343-55. doi: 10.3233/JAD-130578.

Abstract

A systematic approach was used to identify AβPP-selective BACE inhibitors (ASBI) and to evaluate their in vivo ability to modulate AβPP processing selectively. We identified a bioflavonoid nutritional supplement as a molecular lead that acts as an ASBI in cell models, and show that increasing brain levels of this bioflavonoid through a pro-drug approach leads to reduction of Aβ42 in an Alzheimer's disease mouse model. ASBIs represent a novel class of candidate therapeutic agents for Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Aspartic Acid Endopeptidases
  • Brain / drug effects
  • Brain / metabolism
  • Cell Line, Transformed
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Flavonoids / chemistry
  • Flavonoids / pharmacokinetics
  • Flavonoids / pharmacology*
  • Humans
  • Mice
  • Neuregulin-1 / metabolism
  • Protein Binding
  • Rutin / chemistry
  • Rutin / pharmacology
  • Surface Plasmon Resonance
  • Time Factors
  • Transfection

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Flavonoids
  • Neuregulin-1
  • galangin
  • Rutin
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases