The endoplasmic reticulum stress response in neuroprogressive diseases: emerging pathophysiological role and translational implications
journal contribution
posted on 2018-12-01, 00:00 authored by Gerwyn Morris, Basant K Puri, Ken WalderKen Walder, Michael BerkMichael Berk, Brendon Stubbs, Michael Maes, André F CarvalhoThe 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
Journal
Molecular neurobiologyVolume
55Issue
12Pagination
8765 - 8787Publisher
SpringerLocation
New York, N.Y.Publisher DOI
Link to full text
eISSN
1559-1182Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2018, The Author(s)Usage metrics
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Keywords
Endoplasmic reticulum stressMolecular neurobiologyMood disordersNeurodegenerationNeuroprogressionUnfolded protein responseScience & TechnologyLife Sciences & BiomedicineNeurosciencesNeurosciences & NeurologyUNFOLDED-PROTEIN-RESPONSENF-KAPPA-BMITOCHONDRIAL QUALITY-CONTROLPERMEABILITY TRANSITION POREANTIOXIDANT ENZYME-ACTIVITYCYTOSOLIC CALCIUM OVERLOADOXYGEN SPECIES GENERATIONPERK-DEPENDENT ACTIVATIONREDUCES OXIDATIVE STRESSNITRIC-OXIDE SYNTHASE