Activation of PERK signaling attenuates Abeta-mediated ER stress.

Activation of PERK signaling attenuates Abeta-mediated ER stress.

PLoS One. 2010;5(5):e10489

Authors: Lee do Y, Lee KS, Lee HJ, Kim do H, Noh YH, Yu K, Jung HY, Lee SH, Lee JY, Youn YC, Jeong Y, Kim DK, Lee WB, Kim SS

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.

PMID: 20463975 [PubMed - in process]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20463975&dopt=Abstract

Posted 14 May 2010 3:04 AM by pubmed: neuroblastoma
Filed under:

Seten amet diorl oprta ahsellu miokiste porta.

Bean nonumy hendrit mauris phelus porta. Fusce suscipit varius ui. Fusce feugiat malesada odio. Morbi nunc odio, gravida sit cursusnec, luctus aorem. auris phelus porta ae. Fusce suscipit varius ui. Fusce feug.

Read More

There is nothing quite as devastating as hearing that word - neuroblastoma. In seconds your world is turned upside down and your normal life is but a distant memory. You are thrust into a confusing world full of fear. Your child has cancer.

We know. We have been there. The Neuroblastoma Foundation is here for you.

Welcome to our website. It is a place for you to find answers and ask questions. One of the primary goals of the Neuroblastoma Foundation is to ensure that parents, patients and health care professionals find the information they need to make the best treatment decisions possible for children and adults affected by neuroblastoma. There is a vast amount of information throughout the internet, much of which is encapsulated in medical jargon that is so complex that even many medical professionals have difficulty in interpreting its meaning. We are here to help to decipher this information and to make sure you (and your oncologist) understand exactly what it means to you. From treatment decisions to side effects we have parents and experts that have experienced it all and are willing to distill it for you.