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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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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