The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

Morris, Gerwyn and Puri, Basant K. and Walder, Ken and Berk, Michael and Stubbs, Brendon and Maes, Michael and Carvalho, André F. (2018) The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications. Molecular Neurobiology, 55 (12). pp. 8765-8787. ISSN 1559-1182

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Official URL: https://doi.org/10.1007/s12035-018-1028-6

Abstract

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted.

Item Type: Journal Article
Keywords: Neurodegeneration, Neuroprogression, Unfolded protein response, Mood disorders, Endoplasmic reticulum stress, Molecular neurobiology
Faculty: ARCHIVED Faculty of Health, Social Care & Education (until September 2018)
Depositing User: Lisa Blanshard
Date Deposited: 29 Oct 2018 09:39
Last Modified: 14 Nov 2019 16:08
URI: http://arro.anglia.ac.uk/id/eprint/703766

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