control peptide. To determine if cytokines could modify the effects of amyloid 1 42, primary cortical neu rons were pre treated with 1 ng ml individual cytokines, before the addition of 10 M amyloid 1 42. There was no significant difference between the survival of research use neurons pre treated in control medium and those pre treated in medium containing Inhibitors,Modulators,Libraries TNF , IL 1 or IL 6 prior to the addi tion of amyloid 1 42. In contrast, the survival of neurons pre treated with IFN and amyloid 1 42 was significantly less than neurons treated with amyloid 1 42 alone. Further studies demonstrated that this effect of IFN was dose dependent. and a significant reduction in neuro nal survival was still observed when cells were treated with 40 pg per ml of IFN. The effects of IFN were tested on both primary cortical and cerebellar neuronal cultures.

Pre treatment with IFN resulted in reduced Inhibitors,Modulators,Libraries survival of both primary cerebellar and cortical neurons following the addition of 10 M amyloid 1 42. Since it is possible that the effects of IFN in these neuronal cultures were via effects on con IFN on the SH SY5Y neuroblastoma cell line. Pre treat ment with IFN reduced the survival of Inhibitors,Modulators,Libraries SH SY5Y neurob lastoma cells following the addition of 10 M amyloid 1 42 indicating that IFN had a direct effect on neuroblast oma cells. To determine if IFN treated neurons show increased sen sitivity to other neuroto ins, cortical neurons were treated with 100 pg ml of IFN prior to e posure to HuPrP82 146, a synthetic correlate of a neuroto ic peptide found in the brains of patients with prion Inhibitors,Modulators,Libraries disease, stau rosporine or hydrogen pero ide.

The survival of neurons pre treated with IFN was significantly less than that of untreated neurons, when incubated with HuPrP82 146. However, there were no significant differences between the survival of neurons treated with IFN and untreated neurons that were e posed to hydrogen pero ide, or to staurosporine, a drug that caused programmed cell death in neurons via GSK-3 activation of the ceramide pathway. taminating astroglial cells, we also tested the effects of Caspase 3 activity Caspase 3 is an enzyme that is increased during apoptosis and was measured as an alternative indicator of neu ronal injury. Caspase 3 activity was increased in primary cortical neurons treated with amyloid 1 42 or HuPrP82 146, but not in primary cortical neurones treated with control peptides or with IFN alone.

Follow ing pre treatment with 100 pg ml IFN caspase 3 activity in cortical neurons treated with either amyloid 1 42 or HuPrP82 146 was significantly higher than in untreated cells incubated with amyloid 1 42 or HuPrP82 146. IFN raises cytoplasmic PLA2 levels in neurons Since recent p53/MDM2 interaction studies demonstrated that cPLA2 is involved in amyloid 1 42 induced neuronal injury we com pared levels of cPLA2 and another enzyme involved in cell signalling in IFN treated and untreated SH SY5Y cells. Treatment with IFN did not significantly alter Pre treatment with IFN increases HuPrP82 146 induced the total