NNC 26-9100 increases Aβ1-42 phagocytosis, inhibits nitric oxide production and decreases calcium in BV2 microglia cells

Abstract

Microglia are the resident immune cell of the brain involved in the development and progression of Alzheimer’s disease (AD). Modulation of microglia activity represents a potential mechanism for treating AD. Herein, the compound NNC 26–9100 (NNC) was evaluated in toxicity, nitric oxide release, Aβ1–42 uptake and cytosolic calcium assays during lipopolysaccharide (LPS)-activated conditions using mouse BV2 microglia cells. After 24 hours, LPS increased cell toxicity in the alamar blue and lactate dehydrogenase assays, increased nitrite release, and increase cytoplasmic calcium. Addition of NNC decreased the LPS-induce lactate dehydrogenase release, had no effect in the alamar blue assay, decreased nitrite release and decreased cytosolic calcium. In the absence of LPS, NNC increased uptake of FITC-tagged Aβ1–42. These data demonstrate that NNC treatment decreases nitrosative stress and microglia cell damage during LPS-induced activation and enhances phagocytosis of Aβ1–42 during non-inflammatory conditions. Thus, NNC 26–9100 may have beneficial effects in AD and in inflammatory diseases of the brain through enhancement of microglial Aβ clearance, and cell protective effects through prevention of elevated cytosolic calcium and inhibition of nitric oxide release.