The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration
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...
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01607-9 |
| _version_ | 1797789500525510656 |
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| author | Katherine Fodder Rohan de Silva Thomas T. Warner Conceição Bettencourt |
| author_facet | Katherine Fodder Rohan de Silva Thomas T. Warner Conceição Bettencourt |
| author_sort | Katherine Fodder |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T01:51:36Z |
| format | Article |
| id | doaj.art-71a7746b970b45018a1be6dac73ef1f1 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-13T01:51:36Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-71a7746b970b45018a1be6dac73ef1f12023-07-02T11:29:27ZengBMCActa Neuropathologica Communications2051-59602023-06-0111111510.1186/s40478-023-01607-9The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegenerationKatherine Fodder0Rohan de Silva1Thomas T. Warner2Conceição Bettencourt3Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of NeurologyDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of NeurologyQueen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of NeurologyQueen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of NeurologyAbstract 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.https://doi.org/10.1186/s40478-023-01607-9DNA methylationOligodendrocytesNeurodegenerationMyelinEpigeneticsHuman brain |
| spellingShingle | Katherine Fodder Rohan de Silva Thomas T. Warner Conceição Bettencourt The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration Acta Neuropathologica Communications DNA methylation Oligodendrocytes Neurodegeneration Myelin Epigenetics Human brain |
| title | The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration |
| title_full | The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration |
| title_fullStr | The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration |
| title_full_unstemmed | The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration |
| title_short | The contribution of DNA methylation to the (dys)function of oligodendroglia in neurodegeneration |
| title_sort | contribution of dna methylation to the dys function of oligodendroglia in neurodegeneration |
| topic | DNA methylation Oligodendrocytes Neurodegeneration Myelin Epigenetics Human brain |
| url | https://doi.org/10.1186/s40478-023-01607-9 |
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