INTERLEUKIN-1-BETA AND GLUTAMATE ACTIVATE THE NF-KAPPA-B REL BINDING-SITE FROM THE REGULATORY REGION OF THE AMYLOID PRECURSOR PROTEIN GENE IN PRIMARY NEURONAL CULTURES/

We originally reported that members of the family of transcription fac tors NF-kappa B/Rel can specifically recognize two identical sequences , referred to as APP kappa B sites, which are present in the 5'-regula tory region of the APP gene, Here we show that the APP kappa B sites i nteract specifically with a complex which contains one of the subunits of the family, defined as p50 protein, and that they act as positive modulators of gene transcription in cells of neural origin, Additional ly, the nuclear complex specifically binding to the APP kappa B sites is constitutively expressed in primary neurons from rat cerebellum and it is up-regulated in response to both the inflammatory cytokine inte rleukin-1 beta (IL-1 beta) and the excitatory amino acid glutamate. Si nce IL-1, whose levels are known to be induced in brain of individuals affected by Alzheimer's disease, and glutamate, are stimuli which hav e been regarded as major actors on the stage of neurodegenerative proc esses, we believe our evidence as potentially relevant for understandi ng the neuropathology associated with Alzheimer's disease.