The function of p53 and its role in Alzheimer’s and Parkinson’s disease compared to age-related macular degeneration

Abstract

The protein p53 is the main human tumor suppressor. Since its discovery, extensive research has been conducted, which led to the general assumption that the purview of p53 is also essential for additional functions, apart from the prevention of carcinogenesis. In response to cellular stress and DNA damages, p53 constitutes the key point for the induction of various regulatory processes, determining whether the cell induces cell cycle arrest and DNA repair mechanisms or otherwise cell death. As an implication, aberrations from its normal functioning can lead to pathogeneses. To this day, neurodegenerative diseases are considered difficult to treat, which arises from the fact that in general the underlying pathological mechanisms are not well understood. Current research on brain and retina-related neurodegenerative disorders suggests that p53 plays an essential role in the progression of these conditions as well. In this review, we therefore compare the role and similarities of the tumor suppressor protein p53 in the pathogenesis of Alzheimer’s (AD) and Parkinson’s disease (PD), two of the most prevalent neurological diseases, to the age-related macular degeneration (AMD) which is among the most common forms of retinal degeneration.

Altered Glia-Neuron Communication in Alzheimer’s Disease Affects WNT, p53, and NFkB Signaling Determined by snRNA-seq

“…Canonical signaling through the WNT [15, 16], p53 [24], and NFkB [22, 23] signaling pathways have been shown to be dysregulated in AD. The WNT signaling pathway is crucial for normal brain function and neuronal survival in the adult CNS and has been extensively implicated in AD (reviewed in [15, 16]).…”

“…Multiple signaling pathways have been proposed to be dysregulated in AD, including WNT (reviewed in [15,16]), TGFβ (reviewed in [17][18][19]), mTOR (reviewed in [20,21]), NFkB (reviewed in [22,23]), p53 (reviewed in [24]), and Pi3k/Akt signaling (reviewed in [25][26][27]). Recently, multiple computational cell-cell communication (CCC) inference tools, which use single-nucleus RNA-sequencing (snRNA-seq) data to infer ligands and receptors, were developed to predict signaling patterns between cell types (reviewed in [28]).…”

Low-Dose Brain Radiation: Lowering hyperphosphorylated-Tau without Increasing DNA Damage or Oncogenic Activation

“…For example, p53 loss in oligodendrocytes provided protection against subcortical white matter damage and recognition memory impairment in a white matter stroke model [39]. Moreover, various animal studies demonstrated that p53 is elevated during the initial phases of AD and other neurodegenerative conditions [40][41][42][43][44]. Potentially then, sLDR on the entire brain, or a speci c region of it, could have also some possible advantageous effect in terms of p53 reduction in the context of the natural progression of AD and likely other neurodegenerative processes.…”

Doxorubicin impairs cognitive function by upregulating AMPAR and NMDAR subunit expression and increasing neuroinflammation, oxidative stress, and apoptosis in the brain

“…The upregulation of Bax expression elicits the release of cytochrome C, thereby instigating the process of apoptosis through the activation of caspase-3 ( An et al, 2004 ; Mizuta et al, 2007 ). Moreover, the pathogenesis of various disorders, including Alzheimer’s and Parkinson’s disease, can lead to the upregulation of Bax and caspase-3 expression, ultimately resulting in neurodegeneration ( Long et al, 2021 ; Wolfrum et al, 2022 ). In a similar vein, chemotherapeutic agents, such as DOX, have been observed to enhance the expression of Bax and caspase-3, leading to the induction of apoptosis ( Sharifi et al, 2015 ; Singh et al, 2019 ).…”