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

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Coordinating Organismal Physiology Through the Unfolded Protein Response

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 414))

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.

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Acknowledgements

Supported by Millennium Institute No. P09-015-F, FONDAP program 15150012, CONICYT-Brazil 441921/2016-7, ALS Therapy Alliance 2014-F-059, Muscular Dystrophy Association 382453, Michael J. Fox Foundation for Parkinson’s Research—Target Validation grant No 9277, FONDECYT No. 1140549, Office of Naval Research-Global (ONR-G) N62909-16-1-2003, FONDEF D11E1007, U.S. Air Force Office of Scientific Research FA9550-16-1-0384, FONDEF ID16I10223, and ALSRP Therapeutic Idea Award AL150111 (CH). FC is a postdoctoral fellow funded by FONDAP program 15150012.

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Authors and Affiliations

  1. Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile

    Felipe Cabral-Miranda & Claudio Hetz

  2. Faculty of Medicine, Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile

    Felipe Cabral-Miranda & Claudio Hetz

  3. Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Independencia 1027, P.O.BOX 70086, Santiago, Chile

    Felipe Cabral-Miranda & Claudio Hetz

  4. Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Felipe Cabral-Miranda

  5. Buck Institute for Research on Aging, Novato, CA, 94945, USA

    Claudio Hetz

  6. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, 02115, USA

    Claudio Hetz

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  1. Felipe Cabral-Miranda
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  1. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA

    R. Luke Wiseman

  2. Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Cole M. Haynes

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Cabral-Miranda, F., Hetz, C. (2017). ER Stress and Neurodegenerative Disease: A Cause or Effect Relationship?. In: Wiseman, R., Haynes, C. (eds) Coordinating Organismal Physiology Through the Unfolded Protein Response. Current Topics in Microbiology and Immunology, vol 414. Springer, Cham. https://doi.org/10.1007/82_2017_52

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