Open AccessMolecular Investigation of the Unfolded Protein Response in Select Human Tauopathies
Author(s) -
Aleksandra P. Pitera,
Iain James Hartnell,
Lucy Scullard,
Kirsten L. Williamson,
Delphine Boche,
Vincent O’Connor,
Katrin Deinhardt
Publication year - 2021
Publication title -
journal of alzheimer's disease reports
Language(s) - English
Resource type - Journals
ISSN - 2542-4823
DOI - 10.3233/adr-210050
Subject(s) - progressive supranuclear palsy , unfolded protein response , endoplasmic reticulum , cytosol , disease , tau protein , blot , neuroscience , biology , tauopathy , neurodegeneration , microbiology and biotechnology , human brain , alzheimer's disease , medicine , pathology , genetics , biochemistry , gene , enzyme
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.