Molecular investigation of the unfolded protein response in select human tauopathies
Molecular investigation of the unfolded protein response in select human tauopathies
Background: Tauopathies are a group of neurodegenerative diseases associated with the accumulation of misfolded tau protein. The mechanisms underpinning tau-dependent proteinopathy remain to be elucidated. A protein quality control pathway within the endoplasmic reticulum, the unfolded protein response (UPR), has been suggested as a possible pathway modulating cellular responses in a range of neurodegenerative diseases, including those associated with misfolded cytosolic tau.
Objective: In this study we investigated three different clinically defined tauopathies to establish whether these diseases are accompanied by the activation of UPR.
Methods: We used PCR and western blotting to probe for the modulation of several reliable UPR markers in mRNA and proteins extracted from three distinct tauopathies: 20 brain samples from Alzheimer's disease patients, 11 from Pick's disease, and 10 from progressive supranuclear palsy. In each disease samples from these patients were compared with equal numbers of age-matched non-demented controls.
Results: Our investigation showed that different markers of UPR are not changed at the late stage of any of the human tauopathies investigated. Interestingly, UPR signatures were often observed in non-demented controls.
Conclusion: These data from late-stage human cortical tissue report an activation of UPR markers within the aged brain across all cohorts investigated and further support the emerging evidence that the accumulation of misfolded cytosolic tau does not drive a disease-associated activation of UPR.
855-869
Pitera, Aleksandra P
6cf28d67-483b-494b-8323-c01a64c24f71
Hartnell, Iain J
46e8c0a1-f5cc-42f9-bc01-911e2dbf4cce
Scullard, Lucy
f61ff965-ab0f-4210-bef0-7fdad4527a7d
Williamson, Kirsten L
5f005e62-89d5-4c23-9305-324f66795f76
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
9 December 2021
Pitera, Aleksandra P
6cf28d67-483b-494b-8323-c01a64c24f71
Hartnell, Iain J
46e8c0a1-f5cc-42f9-bc01-911e2dbf4cce
Scullard, Lucy
f61ff965-ab0f-4210-bef0-7fdad4527a7d
Williamson, Kirsten L
5f005e62-89d5-4c23-9305-324f66795f76
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Pitera, Aleksandra P, Hartnell, Iain J, Scullard, Lucy, Williamson, Kirsten L, Boche, Delphine, O'Connor, Vincent and Deinhardt, Katrin
(2021)
Molecular investigation of the unfolded protein response in select human tauopathies.
Journal of Alzheimer's disease reports, 5 (1), .
(doi:10.3233/ADR-210050).
Abstract
Background: Tauopathies are a group of neurodegenerative diseases associated with the accumulation of misfolded tau protein. The mechanisms underpinning tau-dependent proteinopathy remain to be elucidated. A protein quality control pathway within the endoplasmic reticulum, the unfolded protein response (UPR), has been suggested as a possible pathway modulating cellular responses in a range of neurodegenerative diseases, including those associated with misfolded cytosolic tau.
Objective: In this study we investigated three different clinically defined tauopathies to establish whether these diseases are accompanied by the activation of UPR.
Methods: We used PCR and western blotting to probe for the modulation of several reliable UPR markers in mRNA and proteins extracted from three distinct tauopathies: 20 brain samples from Alzheimer's disease patients, 11 from Pick's disease, and 10 from progressive supranuclear palsy. In each disease samples from these patients were compared with equal numbers of age-matched non-demented controls.
Results: Our investigation showed that different markers of UPR are not changed at the late stage of any of the human tauopathies investigated. Interestingly, UPR signatures were often observed in non-demented controls.
Conclusion: These data from late-stage human cortical tissue report an activation of UPR markers within the aged brain across all cohorts investigated and further support the emerging evidence that the accumulation of misfolded cytosolic tau does not drive a disease-associated activation of UPR.
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Accepted/In Press date: 14 November 2021
Published date: 9 December 2021
Identifiers
Local EPrints ID: 454854
URI: http://eprints.soton.ac.uk/id/eprint/454854
ISSN: 2542-4823
PURE UUID: cda28055-0866-4cb1-a448-7c8bd2bc4aff
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Date deposited: 25 Feb 2022 18:03
Last modified: 17 Mar 2024 03:30
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Author:
Aleksandra P Pitera
Author:
Iain J Hartnell
Author:
Lucy Scullard
Author:
Kirsten L Williamson
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