p53 Is Regulated by and Regulates Members of the gamma-Secretase Complex

Amyloid beta-peptides is the generic term for a set of hydrophobic peptides that accumulate in Alzheimer's disease (AD)-affected brains. These amyloid-beta peptide fragments are mainly generated by an enzymatic machinery referred to as gamma-secretase complex that is built up by the association of four distinct proteins, namely presenilin 1 (PS1) or PS2, nicastrin, Aph-1 and Pen-2. AD is also characterized by exacerbated cell death that appears linked to the tumor suppressor p53. Interestingly, all members of the gamma-secretase complex control p53-dependent cell death. On the other hand, p53 appears to be able to regulate directly or indirectly the expression and transcription of PS1, PS2 and Pen-2. This review will focus on the functional cross-talk between the members of the gamma-secretase complex and p53 and will discuss the putative implication of this oncogene in AD pathology. Copyright (C) 2010 S. Karger AG, Basel