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International Journal of Cell Biology
Volume 2013, Article ID 674751, 12 pages
Review Article

ER Dysfunction and Protein Folding Stress in ALS

1Neurounion Biomedical Foundation, Santiago, Chile
2Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile
3Center for Molecular Studies of the Cell, Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile
4Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA

Received 22 May 2013; Accepted 2 September 2013

Academic Editor: Roberto Chiesa

Copyright © 2013 Soledad Matus et al. 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.


Amyotrophic lateral sclerosis (ALS) is the most frequent paralytic disease in adults. Most ALS cases are considered sporadic with no clear genetic component. The disruption of protein homeostasis due to chronic stress responses at the endoplasmic reticulum (ER) and the accumulation of abnormal protein inclusions are extensively described in ALS mouse models and patient-derived tissue. Recent studies using pharmacological and genetic manipulation of the unfolded protein response (UPR), an adaptive reaction against ER stress, have demonstrated a complex involvement of the pathway in experimental models of ALS. In addition, quantitative changes in ER stress-responsive chaperones in body fluids have been proposed as possible biomarkers to monitor the disease progression. Here we review most recent advances attributing a causal role of ER stress in ALS.