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Endoplasmic Reticulum Stress and Ethanol Neurotoxicity

Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, 132 Health Sciences Research Building, 1095 Veterans Drive, Lexington, KY 40536, USA
Author to whom correspondence should be addressed.
Academic Editors: Natalia Osna and Kusum Kharbanda
Biomolecules 2015, 5(4), 2538-2553;
Received: 5 August 2015 / Revised: 2 September 2015 / Accepted: 21 September 2015 / Published: 14 October 2015
(This article belongs to the Collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)
Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of unfolded or misfolded proteins in the ER lumen triggers ER stress and induces unfolded protein response (UPR) which are mediated by three transmembrane ER signaling proteins: pancreatic endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6). UPR is initiated to protect cells from overwhelming ER protein loading. However, sustained ER stress may result in cell death. ER stress has been implied in various CNS injuries, including brain ischemia, traumatic brain injury, and aging-associated neurodegeneration, such as Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD). However, effects of ethanol on ER stress in the CNS receive less attention. In this review, we discuss recent progress in the study of ER stress in ethanol-induced neurotoxicity. We also examine the potential mechanisms underlying ethanol-mediated ER stress and the interaction among ER stress, oxidative stress and autophagy in the context of ethanol neurotoxicity. View Full-Text
Keywords: alcohol abuse; ER stress; development; fetal alcohol spectrum disorder; neurodegeneration; neuroprotection alcohol abuse; ER stress; development; fetal alcohol spectrum disorder; neurodegeneration; neuroprotection
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Yang, F.; Luo, J. Endoplasmic Reticulum Stress and Ethanol Neurotoxicity. Biomolecules 2015, 5, 2538-2553.

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