BioProject

The accumulation of amyloid-ß (Aß) peptides in the brain is a crucial step in the pathogenesis of Alzheimer`s disease (AD). More...

The accumulation of amyloid-ß (Aß) peptides in the brain is a crucial step in the pathogenesis of Alzheimer`s disease (AD). Several studies indicate that microglia cells in the brain have the ability to internalize Aß by phagocytosis and might therefore play a protective role in AD. However, the mechanisms underlying Aß clearance remain unresolved. We have found that small molecule inhibitors of the ubiquitous glycogen synthase kinase 3ß (GSK3ß) stimulate the uptake of Aß by human THP-1 monocytes and primary murine microglia cells. To investigate how GSK3ß inhibitors might stimulate Aß uptake, we conducted microarray-based gene expression analyses of THP-1 cells after treatment with three different GSK3ß inhibitors. We identified a subset of genes similarly altered by all three inhibitors, including chemokines and surface receptors that have been linked to the regulation of microglial activation and phagocytosis. Overall design: THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate) were treated for 48h with three different GSK3ß inhibitors (5 µM CHIR99021, 10 µM SB216763, 1 µM Bio-Acetoxime) or DMSO vehicle. RNA was extracted for cDNA synthesis and hybridization on Affymetrix microarrays with two replicates per treatment condition. Less...