Unfolded p53 as a marker of oxidative stress in Mild Cognitive Impairment, Alzheimer’s and Parkinson’s disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Sara García ◽  
Olaya Amor-Gutiérrez ◽  
María Palomares-Albarrán ◽  
Celia Toyos-Rodríguez ◽  
Fernando Cuetos ◽  
...  

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.

2019 ◽  
Vol 34 (8) ◽  
pp. 1244-1250 ◽  
Author(s):  
Eleanor King ◽  
John O'Brien ◽  
Paul Donaghy ◽  
Caroline H. Williams-Gray ◽  
Rachael A. Lawson ◽  
...  

2017 ◽  
Vol 13 (7S_Part_8) ◽  
pp. P416-P416
Author(s):  
Ting Ting Yong ◽  
Russell J. Chander ◽  
Heidi Emmanuel Foo ◽  
Levinia Lim ◽  
Aloysius Yue Tat Ng ◽  
...  

2015 ◽  
Vol 29 (3) ◽  
pp. 112-119 ◽  
Author(s):  
Johann Lehrner ◽  
Harald Krakhofer ◽  
Claus Lamm ◽  
Stefan Macher ◽  
Doris Moser ◽  
...  

2019 ◽  
Vol 20 (18) ◽  
pp. 4432 ◽  
Author(s):  
Jeannie Hwang ◽  
Candice M. Estick ◽  
Uzoma S. Ikonne ◽  
David Butler ◽  
Morgan C. Pait ◽  
...  

Many neurodegenerative disorders have lysosomal impediments, and the list of proposed treatments targeting lysosomes is growing. We investigated the role of lysosomes in Alzheimer’s disease (AD) and other age-related disorders, as well as in a strategy to compensate for lysosomal disturbances. Comprehensive immunostaining was used to analyze brains from wild-type mice vs. amyloid precursor protein/presenilin-1 (APP/PS1) mice that express mutant proteins linked to familial AD. Also, lysosomal modulation was evaluated for inducing synaptic and behavioral improvements in transgenic models of AD and Parkinson’s disease, and in models of mild cognitive impairment (MCI). Amyloid plaques were surrounded by swollen organelles positive for the lysosome-associated membrane protein 1 (LAMP1) in the APP/PS1 cortex and hippocampus, regions with robust synaptic deterioration. Within neurons, lysosomes contain the amyloid β 42 (Aβ42) degradation product Aβ38, and this indicator of Aβ42 detoxification was augmented by Z-Phe-Ala-diazomethylketone (PADK; also known as ZFAD) as it enhanced the lysosomal hydrolase cathepsin B (CatB). PADK promoted Aβ42 colocalization with CatB in lysosomes that formed clusters in neurons, while reducing Aβ deposits as well. PADK also reduced amyloidogenic peptides and α-synuclein in correspondence with restored synaptic markers, and both synaptic and cognitive measures were improved in the APP/PS1 and MCI models. These findings indicate that lysosomal perturbation contributes to synaptic and cognitive decay, whereas safely enhancing protein clearance through modulated CatB ameliorates the compromised synapses and cognition, thus supporting early CatB upregulation as a disease-modifying therapy that may also slow the MCI to dementia continuum.


2016 ◽  
Vol 27 ◽  
pp. 54-60 ◽  
Author(s):  
Lilah M. Besser ◽  
Irene Litvan ◽  
Sarah E. Monsell ◽  
Charles Mock ◽  
Sandra Weintraub ◽  
...  

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