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The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration

Fodder, Katherine; de Silva, Rohan; Warner, Thomas T; Bettencourt, Conceição; (2023) The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration. Acta Neuropathologica Communications , 11 (1) , Article 106. 10.1186/s40478-023-01607-9. Green open access

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Abstract

Neurodegenerative diseases encompass a heterogeneous group of conditions characterised by the progressive degeneration of the structure and function of the central or peripheral nervous systems. The pathogenic mechanisms underlying these diseases are not fully understood. However, a central feature consists of regional aggregation of proteins in the brain, such as the accumulation of β-amyloid plaques in Alzheimer’s disease (AD), inclusions of hyperphosphorylated microtubule-binding tau in AD and other tauopathies, or inclusions containing α-synuclein in Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Various pathogenic mechanisms are thought to contribute to disease, and an increasing number of studies implicate dysfunction of oligodendrocytes (the myelin producing cells of the central nervous system) and myelin loss. Aberrant DNA methylation, the most widely studied epigenetic modification, has been associated with many neurodegenerative diseases, including AD, PD, DLB and MSA, and recent findings highlight aberrant DNA methylation in oligodendrocyte/myelin-related genes. Here we briefly review the evidence showing that changes to oligodendrocytes and myelin are key in neurodegeneration, and explore the relevance of DNA methylation in oligodendrocyte (dys)function. As DNA methylation is reversible, elucidating its involvement in pathogenic mechanisms of neurodegenerative diseases and in dysfunction of specific cell-types such as oligodendrocytes may bring opportunities for therapeutic interventions for these diseases.

Type: Article
Title: The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s40478-023-01607-9
Publisher version: https://doi.org/10.1186/s40478-023-01607-9
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: DNA methylation, Oligodendrocytes, Neurodegeneration, Myelin, Epigenetics, Human brain
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10172702
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