Two Faces of Evil: Cancer and Neurodegeneration

Abstract

Cancers are characterized by enhanced cell survival and altered differ- entiation processes whereas Alzheimer’s disease (AD)-affected brains exhibit exacerbated neuronal loss and cell death. Interestingly, several studies have consis- tently reported on an inverse relationship between cancer and AD. On the other hand, p53, a tumor-suppressor oncogene, is mutated and inactivated in a majority of human cancers; conversely, several lines of evidence concur to suggest an elevation of p53 and its transcriptional targets in AD brains. Therefore, one could envision p53 as a molecular bridge between cancer andADpathologies. Although the role of p53 in cancer likely results from its inactivation by somatic mutations, the mecha- nistic aspects underlying a dysfunction in the control of p53 in AD had not been delineated. Herewe survey recent evidence that p53 could control and be controlled by several members of the presenilin-dependent g-secretase complex, and we briefly discuss the possibility that a functional deficit in presenilins could contribute to the genesis of a subset of tumors