A decay of the adaptive capacity of the unfolded protein response exacerbates Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:63

Editorial Material

Gerakis, Yannis^1,2,3  Hetz, Claudio^1,2,3,4,5 

[1] Univ Chile, Fac Med, Biomed Neurosci Inst, Santiago, Chile

[2] Ctr Gerosci Brain Hlth & Metab, Santiago, Chile

[3] Univ Chile, Inst Biomed Sci, Program Cellular & Mol Biol, Santiago, Chile

[4] Buck Inst Res Aging, Novato, CA USA

[5] Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA

关键词: Alzheimer's disease;    Amyloid beta;    Unfolded protein response;    XBP1;    Neurodegeneration;    Aging;   

DOI  :  10.1016/j.neurobiolaging.2017.09.012

来源: Elsevier

【 摘 要 】

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. (C) 2017 Elsevier Inc. All rights reserved.

【 授权许可】

Free