Mostrar el registro sencillo del ítem

Early and Selective Activation and Subsequent Alterations to the Unfolded Protein Response in Down Syndrome Mouse Models

dc.contributor.authorLanzillotta C.
dc.contributor.authorTramutola A.
dc.contributor.authorMeier S.
dc.contributor.authorSchmitt F.
dc.contributor.authorBarone E.
dc.contributor.authorPerluigi M.
dc.contributor.authorDi Domenico F.
dc.contributor.authorAbisambra J.F.
dc.date.accessioned2020-09-02T22:21:14Z
dc.date.available2020-09-02T22:21:14Z
dc.date.issued2018
dc.identifier10.3233/JAD-170617
dc.identifier.citation62, 1, 347-359
dc.identifier.issn13872877
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5041
dc.descriptionDown syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. DS individuals have an increased risk of developing Alzheimer's disease (AD)-like pathology and dementia by the age of 40 due to the triplication of several genes involved in the formation of amyloid plaques and tau tangles. Further, DS and AD are characterized by the aberrant accumulation of unfolded/misfolded proteins resulting from over-burdened protein quality control systems. The accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers a cellular stress response called the unfolded protein response (UPR). Long-term activation of the UPR mediates neuronal dysfunction in AD. We hypothesized that the UPR is impacted in a mouse model of DS. To test this, we performed gene and protein expression analysis of ER stress markers in the Ts65Dn mouse model of DS at 3, 9, and 18 months. We identified activation of the PERK pathway in Ts65Dn DS mice at 3 months of age compared to euploid controls. We also determined that the early and overt UPR activation decreased with age, the UPR signal was significantly reduced by 18 months. Our data suggest that UPR activation in DS mouse models occurs early before consistent brain neurodegeneration and might be an essential contributor to dys-proteostasis. © 2018-IOS Press and the authors. All rights reserved.
dc.language.isoen
dc.publisherIOS Press
dc.subjectDown syndrome
dc.subjecteif2 alpha
dc.subjectPERK
dc.subjectTs65Dn
dc.subjectunfolded protein response
dc.subjectprotein kinase
dc.subjectprotein kinase RNA like endoplasmic reticulum kinase
dc.subjectunclassified drug
dc.subjectDdit3 protein, mouse
dc.subjectgrowth arrest and DNA damage inducible protein 153
dc.subjectPERK kinase
dc.subjectprotein kinase R
dc.subjectage
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectbrain degeneration
dc.subjectcontrolled study
dc.subjectDown syndrome
dc.subjectendoplasmic reticulum stress
dc.subjectfemale
dc.subjectgene expression
dc.subjectmale
dc.subjectmouse
dc.subjectmouse model
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein homeostasis
dc.subjectunfolded protein response
dc.subjectaging
dc.subjectanimal
dc.subjectdisease exacerbation
dc.subjectdisease model
dc.subjectDown syndrome
dc.subjectgene expression profiling
dc.subjecthippocampus
dc.subjectmetabolism
dc.subjectphysiology
dc.subjecttime factor
dc.subjecttransgenic mouse
dc.subjectunfolded protein response
dc.subjectAging
dc.subjectAnimals
dc.subjectDisease Models, Animal
dc.subjectDisease Progression
dc.subjectDown Syndrome
dc.subjecteIF-2 Kinase
dc.subjectFemale
dc.subjectGene Expression Profiling
dc.subjectHippocampus
dc.subjectMale
dc.subjectMice, Transgenic
dc.subjectTime Factors
dc.subjectTranscription Factor CHOP
dc.subjectUnfolded Protein Response
dc.titleEarly and Selective Activation and Subsequent Alterations to the Unfolded Protein Response in Down Syndrome Mouse Models
dc.typeArticle


Ficheros en el ítem

Thumbnail
Nombre:
item_2-s2.0-85047973196.pdf
Tamaño:
3.984Kb
Formato:
PDF
Ver/

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem