Nuclear factor-kappa B/Rel proteins - A point of convergence of signallingpathways relevant in neuronal function and dysfunction

Nuclear factor-kappa B (NF-kappa B)/Rel designates a family of transcriptio n factors participating in the activation of a wide range of genes cruciall y involved in immune and inflammatory function. NF-kappa B/Rel proteins hav e been demonstrated recently in primary neurons and in several brain areas. Functional significance of these proteins is still not understood complete ly, but since certain subsets of neurons appear to contain constitutively a ctive DNA-binding activity, it seems likely that they may participate in no rmal brain function. A growing body of evidence is accumulating for a speci fic activation of NF-kappa B/Rel proteins in the CNS, and in particular in neuronal cells, during neurodegenerative processes associated to etiologica lly unrelated conditions. Whether NF-kappa B activation is part of the neur odegenerative process or of protective mechanisms is a matter of debate. Th is issue will be reviewed here with particular attention to the available r eports on the activity of NF-kappa B/Rel proteins in both experimental para digms of neurodegeneration and post-mortem brain tissue of patients affecte d by various neurological diseases. We hypothesize that NF-kappa B/Rel prot eins may represent the point of convergence of several signalling pathways relevant for initiating or accelerating the process of neuronal dysfunction and degeneration in many neurological diseases, including Parkinson's dise ase, Alzheimer's disease, CNS viral infections, and possibly others. If NF- kappa B/Rel proteins represent an integrating point of several pathways pot entially contributing to neuronal degeneration, molecules that finely modul ate their activity could represent a novel pharmacological approach to seve ral neurological diseases. (C) 1998 Elsevier Science Inc.