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Activation of p53 in Down Syndrome and in the Ts65Dn Mouse Brain is Associated with a Pro-Apoptotic Phenotype

dc.contributor.authorTramutola A.
dc.contributor.authorPupo G.
dc.contributor.authorDi Domenico F.
dc.contributor.authorBarone E.
dc.contributor.authorArena A.
dc.contributor.authorLanzillotta C.
dc.contributor.authorBroekaart D.
dc.contributor.authorBlarzino C.
dc.contributor.authorHead E.
dc.contributor.authorButterfield D.A.
dc.contributor.authorPerluigi M.
dc.date.accessioned2020-09-02T22:29:23Z
dc.date.available2020-09-02T22:29:23Z
dc.date.issued2016
dc.identifier10.3233/JAD-151105
dc.identifier.citation52, 1, 359-371
dc.identifier.issn13872877
dc.identifier.urihttps://hdl.handle.net/20.500.12728/6436
dc.descriptionDown syndrome (DS) is the most common genetic cause of intellectual disability, resulting from trisomy of chromosome 21. The main feature of DS neuropathology includes early onset of Alzheimer's disease (AD), with deposition of senile plaques and tangles. We hypothesized that apoptosis may be activated in the presence of AD neuropathology in DS, thus we measured proteins associated with upstream and downstream pathways of p53 in the frontal cortex from DS cases with and without AD pathology and from Ts65Dn mice, at different ages. We observed increased acetylation and phosphorylation of p53, coupled to reduced MDM2/p53 complex level and lower levels of SIRT1. Activation of p53 was associated with a number of targets (BAX, PARP1, caspase-3, p21, heat shock proteins, and PGC1α) that were modulated in both DS and DS/AD compared with age-matched controls. In particular, the most relevant changes (increased p-p53 and acetyl-p53 and reduced formation of MDM2/p53 complex) were found to be modified only in the presence of AD pathology in DS. In addition, a similar pattern of alterations in the p53 pathway was found in Ts65Dn mice. These results suggest that p53 may integrate different signals, which can result in a pro-apoptotic-phenotype contributing to AD neuropathology in people with DS. © 2016 IOS Press and the authors. All rights reserved.
dc.language.isoen
dc.publisherIOS Press
dc.subjectApoptosis
dc.subjectcaspase
dc.subjectp53
dc.subjectsirtuins
dc.subjecttrisomy 21
dc.subjectTs65Dn mouse model
dc.subjectcaspase 3
dc.subjectheat shock protein 27
dc.subjectheat shock protein 70
dc.subjectnicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1
dc.subjectperoxisome proliferator activated receptor gamma coactivator 1alpha
dc.subjectprotein Bax
dc.subjectprotein MDM2
dc.subjectprotein p21
dc.subjectprotein p53
dc.subjectsirtuin 1
dc.subjectsirtuin 2
dc.subjectprotein p53
dc.subjectadult
dc.subjectAlzheimer disease
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectDown syndrome
dc.subjectfemale
dc.subjectfrontal cortex
dc.subjecthuman
dc.subjecthuman tissue
dc.subjectmale
dc.subjectmouse
dc.subjectneuropathology
dc.subjectnonhuman
dc.subjectoxidative stress
dc.subjectphenotype
dc.subjectpriority journal
dc.subjectprotein acetylation
dc.subjectprotein phosphorylation
dc.subjectupregulation
dc.subjectacetylation
dc.subjectAlzheimer disease
dc.subjectanimal
dc.subjectapoptosis
dc.subjectC3H mouse
dc.subjectC57BL mouse
dc.subjectdisease model
dc.subjectDown syndrome
dc.subjectfrontal lobe
dc.subjectimmunoprecipitation
dc.subjectmetabolism
dc.subjectmiddle aged
dc.subjectpathology
dc.subjectphenotype
dc.subjectphosphorylation
dc.subjectphysiology
dc.subjecttransgenic mouse
dc.subjectWestern blotting
dc.subjectyoung adult
dc.subjectAcetylation
dc.subjectAlzheimer Disease
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectBlotting, Western
dc.subjectDisease Models, Animal
dc.subjectDown Syndrome
dc.subjectFemale
dc.subjectFrontal Lobe
dc.subjectHumans
dc.subjectImmunoprecipitation
dc.subjectMale
dc.subjectMice, Inbred C3H
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectMiddle Aged
dc.subjectPhenotype
dc.subjectPhosphorylation
dc.subjectTumor Suppressor Protein p53
dc.subjectYoung Adult
dc.titleActivation of p53 in Down Syndrome and in the Ts65Dn Mouse Brain is Associated with a Pro-Apoptotic Phenotype
dc.typeArticle


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