Fig. 6
From: P53 aggregation, interactions with tau, and impaired DNA damage response in Alzheimer’s disease
Proposed mechanism of p53 in Alzheimer’s disease pathology. (Left) Functional p53 response in normal aging where every day cellular stress causes production of DNA damage, p53 is altered by post-translational modifications to move to the nucleus and induce transcription of target genes to ameliorate damage. (Right) In AD disease pathology, the cell becomes stressed and activates p53 to address DNA damage and oxidative stress. However, due to breakdown of the microtubule network and tau oligomer pathology, p53 transport cannot enter the nucleus and accumulates outside the nucleus. Over time p53 may become unstable and start to aggregate. tauO near the nucleus interact with p53, causing sequestration and cross-seeding. P53 that cannot enter the nucleus will result in loss of nuclear function, causing dysfunction in critical cell function such as cell cycle arrest, DNA damage repair, and apoptosis. With no repair nor a way to perform controlled cell death, conditions in the cell will continue to deteriorate, promoting aggregation of other intrinsically disordered proteins