POTENTIAL INVOLVEMENT OF THE TRANSCRIPTION FACTOR NF-KAPPA-B IN NEUROLOGICAL DISORDERS

Reactive oxygen intermediates (ROIs) are involved in many neurological diseases. Despite the toxic nature of these compounds, low concentrations of ROIs can function as signaling molecules. One target for their signaling function is the inducible transcription factor NF-kappaB. Predominantly in lymphoid cells, induction of NF-kappaB in response to oxidative stress leads to transcriptional activation of many genes which are relevant for pathogen defense. These include the TNF, IL-6, IL-8, GM-CSF, beta-interferon, MHC class I and V-CAM genes. However, NF-kappaB is also abundant in various cell types of the nervous system, including neurons. We propose that NF-kappaB plays a role as a redox-controlled transcriptional activator also in cells of the nervous system and in that property may contribute to neurological disorders. Our finding that some neurons from healthy brain contain constitutively active NF-kappaB suggests a role of NF-kappaB in normal brain function as well.