Fig. 2

The p53-Aβ feedback loop revisited. The p53 protein inhibits the amyloid cascade by repressing the transcription of BACE1. Additionally, p53 inhibits the mTOR signaling pathway, resulting in Aβ protein clearance through the induction of autophagy. However, Aβ peptides may prevent these neuroprotective p53 effects through posttranscriptional repression of p53, which leads to reduced binding of p53 to the promotor of the anti-aging gene, SIRT6. Aβ, amyloid beta; AICD, amyloid precursor protein intracellular domain; APP, amyloid precursor protein; BACE1, beta-site APP-cleaving enzyme 1; mTOR, mammalian target of rapamycin; sAPPβ, soluble amyloid precursor protein beta; SIRT6, sirtuin-6