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The graphs in Figure 9 represent p65 staining in the region of DAPI staining for more than 100 cells per treatment group obtained in three independent experiments on at least three different cell preparations as an average SD. Each of Marimastat ic50 the compounds tested resulted in significant translocation of p65 to neuronal nuclei, which exceeded the translocation quantified for TNF. To determine whether our compounds are neuroprotective, we exposed neurons to compound SRI 22782 and glutamate. Treatment of primary neurons at 14 days in vitro with glutamate for 1 hr caused significant cell damage 24 hr following exposure, as assessed by increased levels of extracellular lactate dehydrogenase. When the neurons were pretreated with the maximally effective concentration of SRI 22782 for 24 hr, reduction of 57% in glutamate cytotoxicity was observed. The question of whether Plastid activation of NFB in neurons is prosurvival or prodeath has been very complex undertaking in brain physiology studies. Contradictory reports have been produced, highlighting negative and positive effects of NFB activation on neuronal wellbeing, depending on the activation system used and the specific experimental design. Regardless of the contrasting evidence, clear trend appears establishing that activation of NFB in neurons is usually associated with positive consequences for neuronal resilience and survival in resting and also during exposure to stress. However, the work has been consistently complicated by the fact that selective NFB activation, independently from cytokine receptor activation, is not available at present. Activation of NFB Apogossypolone via cytokine receptor activation is associated with activation of multiple signaling pathways, whose effects are often counteracting each other. For example, activation of the TNF receptor type 1 in neurons is clearly associated with neuroprotective effects, and activation of the TNF type 2 receptor is associated with glial activation of NFB signaling, with nitric oxide increase, proinflammatory and prodeath mechanism. Posttranslational modifications, interaction between NFB subunits and cofactors, as well as novel components of the NFB activation pathways might account for the diverse effects of p65 in neuronal cells. Identification of NFB activating agents based on different noncanonical activation mechanism could represent viable option for exploring the effect of selective NFB p65 activation in neuronal physiology and resilience to injury. In fact, emerging evidence in the literature strongly suggests that enhancing NFB availability using small molecules particularly in neurons may be useful approach in the treatment of neuronal sufferance as it develops in neurodegenerative disorders because it bypasses unwanted effects of cytokine receptor activation.