Transcription factor NF-kappaB: friend or foe of neurons?

It is now well established that a number of neurological disorders such as Parkinson's disease and Alzheimer's disease are characterized by the formation of reactive oxygen species (ROS). When produced in excess, ROS can induce oxidative damage to cellular macromolecules and ultimately cell death. Cells 'employ a number of defense systems against oxidative damage, including antioxidants and antioxidant enzymes. In an effort to develop a better understanding of the molecular mechanisms of the cellular response to a challenge by ROS as observed under certain neuropathological conditions, recent studies have focused on the regulation of gene expression by neurotoxins, including oxidative stressors. One transcription factor that can be activated by oxidative stress is the nuclear transcription factor-kappa B (NF-kappaB). Initially, this factor has been shown to play a major role in the activation of defensive genes during immune and inflammatory responses. But as evidence accumulates suggesting a close association of NF-kappaB activation also with the neuropathology occurring in neurodegenerative processes and neuronal cell death, the search is on to define potential roles for this transcription factor that are specific for neurons. The present article summarizes some of the recent studies that are trying to clarify NF-kappaB's role during neuronal degeneration.