Document Detail


Targeting endoplasmic reticulum stress in metabolic disease.
MedLine Citation:
PMID:  23324104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Endoplasmic reticulum (ER) stress, a condition that dramatically affects protein folding homeostasis in cells, has been associated with a number of metabolic diseases. Emerging preclinical and clinical evidence supports the notion that pharmacological modulators of ER stress have therapeutic potential as novel treatments of metabolic disorders.
AREAS COVERED: In this review, the molecular mechanisms of ER stress and the unfolded protein response (UPR) in the pathogenesis of metabolic diseases are discussed, highlighting the roles of various UPR components revealed using disease models in mice. Special emphasis is placed on the use of novel small molecules in animal disease models and human pathologies, including type 2 diabetes, obesity, fatty liver disease, and atherosclerosis.
EXPERT OPINION: ER stress is a highly promising therapeutic target for metabolic disease. Small molecular chemical chaperones have already demonstrated therapeutic efficacy in animal and human studies. The emergence of compounds that target specific UPR signaling pathways will provide more options for this purpose. Although the findings are promising, more studies are needed to elucidate the efficacy and side effects of these small molecules for future use in humans.
Authors:
Stewart Siyan Cao; Randal J Kaufman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2013-01-17
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  17     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-15     Completed Date:  2013-08-28     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  437-48     Citation Subset:  IM    
Affiliation:
Del E. Webb Neuroscience, Aging and Stem Cell Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology,  therapeutic use
Apoptosis / drug effects
Endoplasmic Reticulum Stress / drug effects*
Humans
Metabolic Diseases / drug therapy*,  metabolism
Molecular Targeted Therapy*
Signal Transduction / drug effects*
Unfolded Protein Response / drug effects
Grant Support
ID/Acronym/Agency:
P01HL057346R01/HL/NHLBI NIH HHS; R01DK088227/DK/NIDDK NIH HHS; R01HL052173/HL/NHLBI NIH HHS; R24DK093074/DK/NIDDK NIH HHS; R37DK042394/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants

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