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Activation of PERK Signaling Attenuates Aβ-Mediated ER Stress

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dc.contributor.authorLee, Do Yeon-
dc.contributor.authorLee, Kyu-Sun-
dc.contributor.authorLee, Hyun Jung-
dc.contributor.authorKim, Do Hee-
dc.contributor.authorYu, Kweon-
dc.contributor.authorLee, Sang Hyung-
dc.contributor.authorYoun, Young Chul-
dc.contributor.authorKim, Dae Kyong-
dc.contributor.authorKim, Sung Su-
dc.contributor.authorLee, Won Bok-
dc.contributor.authorJeong, Yoonhwa-
dc.contributor.authorLee, Jun Young-
dc.contributor.authorJung, Hee-Yeon-
dc.contributor.authorNoh, Yoo Hun-
dc.identifier.citationPLOS ONE; Vol.5 5; e10489ko_KR
dc.description.abstractAlzheimer`s disease (AD) is characterized by the deposition of aggregated beta-amyloid (A β), 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 Aβ neurotoxicity still remain unknown. Here, we show that treatment of Aβ triggers the UPR in the SK-N-SH human neuroblastoma cells. Aβ mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2α pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Aβ neurotoxicity through reducing the activation of eIF2α and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2α pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Aβ treated neurons. These results indicate that PERK-eIF2α pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD.ko_KR
dc.description.sponsorshipThis work was supported by a grant from the BioGreen 21 Program (No. 20100301061075), Rural Development Administration, Republic of Korea. The
funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.titleActivation of PERK Signaling Attenuates Aβ-Mediated ER Stressko_KR
dc.citation.journaltitlePLOS ONE-
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