Notch signaling proteins HES-1 and Hey-1 bind to insulin degrading enzyme (IDE) proximal promoter and repress its transcription and activity: Implications for cellular Aβ metabolism

► We determined IDE transcript levels in human brain and cell cultures over-expressing NICD, HES-1 or Hey-1 cDNAs. ► We detected extracellular Aβ accumulation in N2aSW cells after NICD or Hey-1 transfection. ► HES-1 and Hey-1 bind to the consensus domain located at position − 310/− 305 of human IDE promoter. ► Site-directed mutagenesis of the − 310/− 305 binding site reverts the inhibition of IDE transcription ► Notch signaling exerts an inhibitory effect on IDE transcription in vitro (N2aSW cells) and in vivo (Tg2576 mice).