Phenotypic assays for β-amyloid in mouse embryonic stem cell-derived neurons. Academic Article uri icon

Overview

abstract

  • Given the complex nature of Alzheimer's disease (AD), a cell-based model that recapitulates the physiological properties of the target neuronal population would be extremely valuable for discovering improved drug candidates and chemical probes to uncover disease mechanisms. We established phenotypic neuronal assays for the biogenesis and synaptic action of amyloid β peptide (Aβ) based on embryonic stem cell-derived neurons (ESNs). ESNs enriched with pyramidal neurons were robust, scalable, and amenable to a small-molecule screening assay, overcoming the apparent limitations of neuronal models derived from human pluripotent cells. Small-molecule screening of clinical compounds identified four compounds capable of reducing Aβ levels in ESNs derived from the Tg2576 mouse model of AD. Our approach is therefore highly suitable for phenotypic screening in AD drug discovery and has the potential to identify therapeutic candidates with improved efficacy and safety potential.

publication date

  • July 25, 2013

Research

keywords

  • Amyloid beta-Peptides
  • Drug Evaluation, Preclinical
  • Embryonic Stem Cells
  • Neurons
  • Phenotype

Identity

PubMed Central ID

  • PMC3780781

Scopus Document Identifier

  • 84880890325

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2013.06.005

PubMed ID

  • 23890013

Additional Document Info

volume

  • 20

issue

  • 7