Walker, C. and El-Khamisy, S.F. orcid.org/0000-0003-2721-7763 (2018) Perturbed autophagy and DNA repair converge to promote neurodegeneration in amyotrophic lateral sclerosis and dementia. Brain, 141 (5). pp. 1247-1262. ISSN 0006-8950
Abstract
Maintaining genomic stability constitutes a major challenge facing cells. DNA breaks can arise from direct oxidative damage to the DNA backbone, the inappropriate activities of endogenous enzymes such as DNA topoisomerases, or due to transcriptionallyderived RNA/DNA hybrids (R-loops). The progressive accumulation of DNA breaks has been linked to several neurological disorders. Recently, however, several independent studies have implicated nuclear and mitochondrial genomic instability, perturbed co-transcriptional processing, and impaired cellular clearance pathways as causal and intertwined mechanisms underpinning neurodegeneration. Here, we discuss this emerging paradigm in the context of amyotrophic lateral sclerosis and frontotemporal dementia, and outline how this knowledge paves the way to novel therapeutic interventions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | R-loops; autophagy; DNA repair; genomic instability; neurodegeneration |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Funding Information: | Funder Grant number LISTER INSTITUTE OF PREVENTATIVE MEDICINE NONE WELLCOME TRUST (THE) 103844/Z/14/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Sep 2018 14:50 |
Last Modified: | 19 Sep 2018 14:50 |
Published Version: | https://doi.org/10.1093/brain/awy076 |
Status: | Published |
Publisher: | Oxford University Press |
Refereed: | Yes |
Identification Number: | 10.1093/brain/awy076 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:133520 |