One Path to Cell Death in the Nervous System

Both acute and chronic insults to the nervous system can result in changes in homeostasis that result in cell death or recovery processes that alter function. The signaling mechanisms for this broad spectrum of events that impair neurological function span the gamut from abrupt injury to the slow onset of neurodegenerative diseases in extreme aging. A common element in all of these events is the triggering of signal cascades that determine cellular commitment to apoptosis as a ameliorative alternative to inflammatory necrosis. Key in these cascades is the activation of the caspase and Bcl-family of proteins by the NF-κB transcription factor. Here we consider aspects of specificity of activation as a result of the differential expression of NF-κB proteins and their regulation of selective genes as a result of binding to select DNA consensus sequences out of the 64 different combinations that constitute the NF-κB DNA binding consensus sequence.