Glimepiride reduces CD14 expression and cytokine secretion from macrophages

Background Activated microglia are associated with deposits of aggregated proteins within the brains of patients with Alzheimer’s disease (AD), Parkinson’s disease (PD) and prion diseases. Since the cytokines secreted from activated microglia are thought to contribute to the pathogenesis of these neurodegenerative diseases, compounds that suppress cytokine production have been identified as potential therapeutic targets. CD14 is a glycosylphosphatidylinositol (GPI)- anchored protein that is part of a receptor complex that mediates microglial responses to peptides that accumulate in prion disease (PrP82-146), AD (amyloid-β (Aβ)42) and PD (α-synuclein (αSN)). As some GPI-anchored proteins are released from cells by treatment with glimepiride, a sulphonylurea used for the treatment of diabetes, the effects of glimepiride upon CD14 expression and cytokine production from cultured macrophages were studied.