Activation of PERK Signaling Attenuates Aβ-Mediated ER Stress

• DOI: 10.1371/journal.pone.0010489
• Publication Date: 2010-05-05T16:55:48Z
• Authors: Do Yeon Lee; Kyu-Sun Lee; Hyun Jung Lee; Do Hee Kim; Yoo Hun Noh; Kweon Yu; Hee-Yeon Jung; Sang Hyung Lee; Jun Young Lee; Young Chul Youn; Yoonhwa Jeong; Dae Kyong Kim; Won Bok Lee; Sung Su Kim
• Keywords: ATF4; Neurotoxicity; Caspase 12; Integrated stress response; Tauroursodeoxycholic acid

Alzheimer's disease (AD) is characterized by the deposition of aggregated beta-amyloid (Aβ), which triggers a cellular stress response called unfolded protein (UPR). The UPR signaling pathway defense system for dealing with accumulation misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) prolonged. ER involved in neurodegenerative diseases including AD, molecular mechanisms stress-mediated Aβ neurotoxicity still remain unknown. Here, we show that treatment SK-N-SH human neuroblastoma cells. mediated accompanies activation protective pathways such as Grp78/Bip and PERK-eIF2α pathway, well apoptotic CHOP caspase-4. Knockdown PERK enhances through reducing eIF2α Grp8/Bip neurons. Salubrinal, an activator significantly increased chaperone resulted attenuating caspase-4 dependent treated These results indicate potential target therapeutic applications AD.