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Int. J. Mol. Sci. 2015, 16(4), 7133-7142; doi:10.3390/ijms16047133

Unfolding the Unfolded Protein Response: Unique Insights into Brain Ischemia

1
Cardiovascular Research Institute and Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
2
Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA
3
Cardiovascular Research Institute and Departments of Emergency Medicine and Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Xiaofeng Jia
Received: 29 January 2015 / Revised: 19 March 2015 / Accepted: 27 March 2015 / Published: 30 March 2015
(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)
View Full-Text   |   Download PDF [1109 KB, uploaded 30 March 2015]   |  

Abstract

The endoplasmic reticulum (ER) is responsible for processing of proteins that are destined to be secreted, enclosed in a vesicle, or incorporated in the plasma membrane. Nascent peptides that enter the ER undergo a series of highly regulated processing steps to reach maturation as they transit the ER. Alterations in the intracellular environment that induce ER stress are thought to interrupt these processing steps, and result in unfolding of proteins in the ER. Accumulation of unfolded proteins concurrently activates three transmembrane stress sensors, IRE1, ATF6 and PERK, and is referred to as the Unfolded Protein Response (UPR). Our understanding of the mechanisms of UPR induction has been assembled primarily from experiments inducing ER stress with chemical and genetic manipulations. However, physiological stress often induces activation of ER stress sensors in a distinct manner from the canonical UPR. The unique activation profiles in vivo have prompted us to examine the mechanism of UPR activation in neurons following cerebral ischemia. View Full-Text
Keywords: cardiac arrest; brain ischemia; unfolded protein response; PKR-Like Endoplasmic Reticulum Kinase (PERK); Inositol Requiring Enzyme 1 (IRE1); Activating Transcription Factor 6 (ATF6); Glucose-Regulated Protein 78/Binding Protein (GRP78/BiP) cardiac arrest; brain ischemia; unfolded protein response; PKR-Like Endoplasmic Reticulum Kinase (PERK); Inositol Requiring Enzyme 1 (IRE1); Activating Transcription Factor 6 (ATF6); Glucose-Regulated Protein 78/Binding Protein (GRP78/BiP)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Sanderson, T.H.; Gallaway, M.; Kumar, R. Unfolding the Unfolded Protein Response: Unique Insights into Brain Ischemia. Int. J. Mol. Sci. 2015, 16, 7133-7142.

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