Role of p53 in neurodegenerative diseases

Abstract

Background: p53 plays an important role in many areas of cellular physiology and biology, ranging from cellular development and differentiation to cell cycle arrest and apoptosis. Many of its functions are attributed to its role in assuring proper cellular division. However, since the establishment of its role in cell cycle arrest, damage repair, and apoptosis (thus also establishing its importance in cancer development), numerous reports have demonstrated additional functions of p53 in various cells. In particular, p53 appears to have important functions as it relates to neurodegeneration and synaptic plasticity.

Objective: In this review, we will address p53 functions as it relates to various neurodegenerative diseases, mainly its implications in the development of HIV-associated neurocognitive disorders.

Conclusion: p53 plays a pivotal role in the development of neurodegenerative diseases through its interaction with cellular factors, viral factors, and/or small RNAs that have the ability to promote the development of these diseases. Hence, inhibition of p53 may present an ideal target to restore neuronal functions.

Fig. 1

Brain areas affected by neurodegenerative diseases. Schematic representation (coronal section through caudal parts of the ventral lateral nucleus, massa intermedia, and basilar pons) of the brain areas that are initially damaged by various neurodegenerative diseases. The names of the affected areas are marked (X).

Fig. 2

p53 activation pathways. Schematic representation of the pathways activated by HIV-1 viral proteins to induce p53 levels. Small non-coding RNAs such as miR-34a are also involved in these pathways in neuronal cells. It is unclear whether Nef protein is also using miRNAs to regulate p53 levels.