NF-κB signaling pathway. The transcription factor NF-κB is constitutively expressed in the central nervous system (CNS), where it can be activated by several stimuli, including TNFα, opioids, β-amyloid, and sAPP, to name a few. The NF-κB complex is sequestered in a dimer form (with p65/p50 dimers as the most common composition) in the cytoplasm, where it is bound by IκB. Upon activation by various stimuli, IKK interacts with the inhibitory IκB, resulting in phosphorylation, ubiquitination, and degradation of IκB, rendering the dimer free to translocate to the nucleus. Here, the dimer binds to kappa B binding sites of several gene targets that may be involved in cell survival in neurons or inflammatory pathways in glia. Dimers consisting of p65/p50 tend to be transcriptionally active, whereas p50 homodimers tend to suppress gene transcription. Red text indicates methods appropriate to investigate specific components of NF-κB signaling. BDNF = brain-derived neurotrophic factor; CaMKII = calcium-calmodulin kinase II; ChIP = chromatin immunoprecipitation; ELISA = enzyme-linked immunosorbent assay; EMSA = gel electrophoresis mobility shift assay; IκB = inhibitory κB protein; IKK = inhibitory κB protein kinase; MnSOD = manganese superoxide dismutase; PCR = polymerase chain reaction; PSD-95 = postsynaptic density protein-95; sAPP = secreted amyloid precursor protein; TNFα = tumor necrosis factor alpha.