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.

STAT1-induced ASPP2 transcription identifies a link between neuroinflammation, cell polarity, and tumor suppression

“…Several studies have attributed p53-mediated apoptosis to a number of acute and chronic neurodegenerative disorders, including excitotoxicity, AD, Parkinson disease, multiple sclerosis, and Huntington disease (3). Accumulating evidence supports the role of reactive oxygen species in prompting DNA damage in neurodegenerative disease (4), leading to p53-dependent apoptosis.…”

The Machado–Joseph Disease Deubiquitinase Ataxin-3 Regulates the Stability and Apoptotic Function of p53

“…For example, p53 was found to be highly elevated in brains affected by several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), HIV-associated neurocognitive disorders (HAND), etc. [59]. Furthermore, several epidemiological studies have found an inverse correlation between the risk of developing neurodegenerative disorders and cancer [60–62], suggesting that some common protein effectors might likely be involved between these two multifactorial chronic pathologies.…”

The P72R Polymorphism of p53 Predisposes to Obesity and Metabolic Dysfunction

“…This protein confers its tumor suppressive activities predominantly by acting as a transcription factor, transactivating over two hundred different target genes. p53 has also been found to be a critical factor governing innate and adaptive immune responses, reproduction, development, neural degeneration and aging (Chang et al, 2012; Danilova et al, 2008; Levine et al, 2011; Menendez et al, 2013; Poyurovsky and Prives, 2010). More recently, the relationship between p53 and metabolism has become the focus of new studies, particularly with the revelation that the role of p53 in metabolism may be essential to its tumor suppressor function (Li et al, 2012; Long et al, 2013; Maddocks et al, 2013; Vousden and Ryan, 2009).…”