Anglia Ruskin Research Online (ARRO)
Browse
Stubbs_2018_2.pdf (1.28 MB)

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

Download (1.28 MB)
journal contribution
posted on 2023-07-26, 14:28 authored by Gerwyn Morris, Basant K. Puri, Ken Walder, Michael Berk, Brendon Stubbs, Michael Maes, André F. Carvalho
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.

History

Refereed

  • Yes

Volume

55

Issue number

12

Page range

8765-8787

Publication title

Molecular Neurobiology

ISSN

1559-1182

Publisher

Springer

File version

  • Published version

Language

  • eng

Legacy posted date

2018-10-29

Legacy creation date

2018-10-29

Legacy Faculty/School/Department

ARCHIVED Faculty of Health, Social Care & Education (until September 2018)

Usage metrics

    ARU Outputs

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC