Article

NUCLEAR FACTOR-κ B REGULATES βAPP AND β-AND γ-SECRETASES DIFFERENTLY AT PHYSIOLOGICAL AND SUPRAPHYSIOLOGICAL Aβ CONCENTRATIONS

Journal of Biological Chemistry (Impact Factor: 4.57). 05/2012;

ABSTRACT Background: NF-κB regulates BACE1 but few data concern βAPP and γ-secretase. Results: NF-κB differently regulates Aβ production at physiological and supraphysiological Aβ concentrations by modulating transactivations of βAPP and γ-secretase promoters thereby controlling γ-secretase activity. Conclusion: In physiological conditions, NF-κB regulates Aβ homeostasis while it contributes to increase Aβ production in pathological context. Significance: NF-κB could be seen as a potential therapeutic target. ABSTRACT Anatomical lesions in Alzheimer's disease-affected brains mainly consist in senile plaques, inflammation stigmata and oxidative stress. The nuclear factor-κB (

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