A decay of the adaptive capacity of the unfolded protein response exacerbates Alzheimer's disease
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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.
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
Artículo de publicación ISI
Quote ItemNeurobiology of Aging, 63 (2018): 162-164
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