A decay of the adaptive capacity of the unfolded protein response exacerbates Alzheimer's disease
Author
dc.contributor.author
Gerakis, Yannis
Author
dc.contributor.author
Hetz Flores, Claudio
Admission date
dc.date.accessioned
2018-07-27T19:24:01Z
Available date
dc.date.available
2018-07-27T19:24:01Z
Publication date
dc.date.issued
2018
Cita de ítem
dc.identifier.citation
Neurobiology of Aging, 63 (2018): 162-164
es_ES
Identifier
dc.identifier.other
10.1016/j.neurobiolaging.2017.09.012
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/150396
Abstract
dc.description.abstract
Alterations in the buffering capacity of the proteostasis network are a salient feature of Alzheimer's disease, associated with the occurrence of chronic endoplasmic reticulum (ER) stress. To cope with ER stress, cells activate the unfolded protein response (UPR), a signal transduction pathway that enforces adaptive programs through the induction of transcription factors such as X-box binding protein 1 (XBP1). A new study by Marcora et al used a fly model to study amyloid beta pathogenesis in the secretory pathway of neurons. Through genetic manipulation, authors identified a new role of XBP1s in the clearance of amyloid beta and the improvement of neuronal function. However, although the activation of the UPR signaling was sustained over time, the transcriptional upregulation of XBP1-target genes was attenuated during aging. This study suggests that aging has a negative impact in the ability of the UPR to manage proteostasis alterations in Alzheimer's disease.
es_ES
Patrocinador
dc.description.sponsorship
FONDAP
15150012
US Office of Naval Research-Global (ONR-G)
N62909-16-1-2003
Millennium Institute
P09-015-F
FONDEF
ID16I10223
D11E1007
US Air Force Office of Scientific Research
FA9550-16-1-0384
CONICYT-Brazil
441921/2016-7