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Title 

Activation of PERK signaling attenuates Abeta-mediated ER stress

 

Abeta에 의해 유도되는 ER stress를 억제하는 PERK

Authors 

Do Yeon LeeKyu-Sun LeeH J LeeD H KimY H NohKweon YuH Y JungS H LeeJ Y LeeY C YounY JeongD K KimW B LeeS S Kim

Publisher 

Public Library of Science

Issue Date 

2010

Citation 

Plos One, vol. 5, no. 5, pp. e10489-e10489

Abstract 

Alzheimer's disease (AD) is characterized by the deposition of aggregated beta-amyloid (Abeta), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of ER stress-mediated Abeta neurotoxicity still remain unknown. Here, we show that treatment of Abeta triggers the UPR in the SK-N-SH human neuroblastoma cells. Abeta mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2alpha pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Abeta neurotoxicity through reducing the activation of eIF2alpha and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2alpha pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Abeta treated neurons. These results indicate that PERK-eIF2alpha pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD.

ISSN 

1932-6203

Link 

http://dx.doi.org/10.1371/journal.pone.0010489

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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