Unfolded p53 as a Marker of Oxidative Stress in Mild Cognitive Impairment, Alzheimer’s and Parkinson’s Disease

Abstract

Aims: There are several candidate biomarkers for AD and PD which differ in sensitivity, specificity, cost-effectiveness, invasiveness, logistical and technical demands. This study is aimed to test whether plasma concentration of unfolded p53 may help to discriminate among the neurodegenerative processes occurring in Mild Cognitive Impairment, Alzheimer’s disease and Parkinson's disease. Method: An electrochemical immunosensor was used to measure unfolded p53 in plasma samples of 20 Mild Cognitive Impairment (13 males/7 females; mean age 74.95±5.31), 20 Alzheimer’s (11 males/9 females; mean age: 77.25±7.79), 15 Parkinson’s disease patients (12 males/3 females; mean age: 68.60 ± 7.36) and its respective age/sex/studies-matched controls. Result: We observed a significantly higher concentration of unfolded p53 in the plasma of patients of each of the three pathologies with respect to their control groups (p=0.000). Furthermore, the plasma concentration of unfolded p53 was significantly higher in Alzheimer’s disease patients in comparison with Mild Cognitive Impairment patients (p=0.000) and Parkinson’s disease patients (p=0.006). No significant difference between Mild Cognitive Impairment and Parkinson’s disease patients was observed (p=0.524). Conclusion: Our results suggest that unfolded p53 concentration in the plasma may be a useful biomarker for an undergoing neuropathological process that may be common, albeit with a different intensity, to different diseases.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…Up to now, lipid peroxidation and many oxidative-stress-related molecules have been detected as differentially expressed in AD brain, urine, and/or CSF compared to controls, such as 3-nitrotyrosine, 4-hydroxynonenal, and 8-hydroxy-2-deoxyguanosine [ 161 , 162 ]. Recently, blood has also been considered a source for oxidative-stress-based biomarkers, and Table 1 summarizes the main findings [ 10 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 ].…”

“…Other potential markers directly or indirectly associated with oxidative stress imbalance, such as sialic acid deficiency, increased protein carbonylation, plasma unfolded p53, acetylcholinesterase (AChE) expression, serum thiol–disulfide balance, and serum ischemia-modified albumin (IMA) concentration, have been investigated in independent studies, but their results need to be replicated [ 10 , 172 , 189 , 190 , 191 ]. Interestingly, when 113 patients with aMCI were compared to 832 controls, serum IMA amount, and the IMA/albumin ratio, were shown to be capable of detecting AD at the prodromal stage, suggesting the potential for this molecule to detect early disease onset [ 172 ].…”

“…A biomarker can be defined as a biological marker capable of indicating molecular changes both at a physiological and pathological level [ 8 , 9 ]. An ideal biomarker should be reproducible, highly accurate, non-invasive, cost-effective, easy and quick to measure, and capable of distinguishing between similar conditions without exaggerated technical demand [ 8 , 9 , 10 ]. Regarding AD, although extensive research has been carried out on Aβ and tau protein alteration in the cerebrospinal fluid (CSF) and via positron emission tomography (PET), high invasiveness and considerable costs remain a concern, thus preventing the implementation of large-scale population screenings [ 11 ].…”

Serum metabolomics analysis combined with network pharmacology reveals possible mechanisms of postoperative cognitive dysfunction in the treatment of Mongolian medicine Eerdun Wurile basic formula

“…Activation of p53 occurs through multiple mechanisms, including phosphorylation of ATM, ATR, Chk1, and MAPK, which induce cellcycle arrest, apoptosis, senescence, DNA repair, or metabolic changes (Polato et al, 2014). Studies suggest that plasma concentrations of unfolded p53 may be a useful biomarker of ongoing neuropathological processes and help distinguish between neurodegenerative processes occurring in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease (García et al, 2021). In addition, showed that the BaZiBuShen formula may reduce premature aging by Wnt-responsive genes, leading to changes in the expression of different target genes (Satow et al, 2012;Yu et al, 2012).…”

Circular RNAs in Parkinson’s Disease: Reliable Biological Markers and Targets for Rehabilitation

“…Recent investigations in cellular and animal models of PD as well as in the brains of PD patients have demonstrated that p53 levels and activity are markedly elevated in affected neurons. Activation of p53 in response to neurodegenerative stress is closely associated with reactive oxygen species (ROS) production, abnormal protein aggregation and autophagic damage to dopaminergic neurons degeneration, and these pathogenic events are relevant to the pathogenesis of PD[59]. Meanwhile p53 is a transcription factor that regulatesmitochondrial stability and normal cell growth.…”