Aspirin inhibits cytotoxicity of prion peptide PrP106-126 to neuronal cells associated with microglia activation in vitro

The synthetic peptide consisting of amino acid residues 106-126 of the human prion protein PrP106-126 has been demonstrated to generate fibrils, which damage neurons either directly by interacting with components of the cell surface to trigger cell apoptosis signaling or indirectly by activating microglia to produce inflammatory mediators. In our study, rat microglia cells were treated with PrP106-126 or scramble PrP106-126 (Scr PrP). Activated nuclear factor κB (NF-κB) was determined using immunofluorescence staining and the expression of TNF-α and IL-1β mRNA was measured by quantitative RT-PCR. Inhibitory activity of aspirin on neurotoxicity of PrP106-126 associated with microglia activation was determined using an apoptosis detection kit. Treatment of microglia with 25 μM PrP106-126, but not Scr PrP, resulted in activation and translocation of NF-κB, which peaked after 20 min of treatment. The activation of NF-κB was followed by increased mRNA expression of TNF-α and IL-1β peaking at about 20 h. In the presence of microglia, aspirin significantly inhibited neuro-2a cell death induced by PrP106-126. The number of neuro-2a cells in apoptosis and necrosis with 5 mM aspirin was about 3-fold lower than the cell culture without aspirin (P < 0.05). These data suggest that increased production of cytokines by microglia cells in prion disease is probably regulated by NF-κB translocation and may contribute to neurotoxicity of prions, and neurotoxicity of PrP106-126 may be inhibited by aspirin.