NF-κB in neurons-mechanisms and myths

The transcriptional activation of specific genes by transciption factor proteins is an important factor in the determination of cell-type specific patterns of gene expression. In one form or another, transcription factors comprising the Rel-family of proteins (responsible for the activity referred to as "NF-κB") are present in every cell type examined. However, studies of NF-κB often rely solely on a single endpoint (e.g., nuclear translocation) as an index of activation. Careful examination of CNS neuronal populations indicates that the initial components of NF-κB activation, up to and including nuclear translocation, are often dissociated from transcriptional activation. Indeed, there are few, if any, circumstances in which classical transcriptional activation by NF-κB has been documented in CNS neurons. In addition to the mechanistic intrigue this disjunction inspires, it is possible that this phenomenon contributes to important cell-type specificity distinguishing neurons from other cell types. It also suggests several implications for pharmacotherapeutic manipulation of NF-κB in the CNS.