Post-translational Modifications of the p53 Protein and the Impact in Alzheimer’s Disease: A Review of the Literature

Abstract

Our understanding of Alzheimer’s disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses. More recently, the p53 protein, well-known as a genome guardian, has gained attention for its potential role in the early evolution of AD. This is due to the central involvement of p53’s in the control of oxidative stress and potential involvement in the Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can affect brain processes, thus contributing to AD development. The following review will explore the impact of p53 PTMs on its function and consequential involvement in AD pathogenesis. The greater understanding of the role of p53 in the pathogenesis of AD could result in more targeted therapies benefiting the many patients of this debilitating disease.