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Curr Top Microbiol Immunol. 2018;414:131-157. doi: 10.1007/82_2017_52.

ER Stress and Neurodegenerative Disease: A Cause or Effect Relationship?

Cabral-Miranda F1,2,3,4, Hetz C5,6,7,8,9.

Author information

1
Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile.
2
Faculty of Medicine, Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile.
3
Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Independencia 1027, P.O.BOX 70086, Santiago, Chile.
4
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
5
Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile. chetz@med.uchile.cl.
6
Faculty of Medicine, Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile. chetz@med.uchile.cl.
7
Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Independencia 1027, P.O.BOX 70086, Santiago, Chile. chetz@med.uchile.cl.
8
Buck Institute for Research on Aging, Novato, CA, 94945, USA. chetz@med.uchile.cl.
9
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, 02115, USA. chetz@med.uchile.cl.

Abstract

The accumulation of protein aggregates has a fundamental role in the patophysiology of distinct neurodegenerative diseases. This phenomenon may have a common origin, where disruption of intracellular mechanisms related to protein homeostasis (here termed proteostasis) control during aging may result in abnormal protein aggregation. The unfolded protein response (UPR) embodies a major element of the proteostasis network triggered by endoplasmic reticulum (ER) stress. Chronic ER stress may operate as possible mechanism of neurodegenerative and synaptic dysfunction, and in addition contribute to the abnormal aggregation of key disease-related proteins. In this article we overview the most recent findings suggesting a causal role of ER stress in neurodegenerative diseases.

PMID:
28864830
DOI:
10.1007/82_2017_52
[Indexed for MEDLINE]

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