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

Acta Neuropathologica Communications

Review

Rohan de Silva¹  Thomas T. Warner²  Conceição Bettencourt³  Katherine Fodder³ 

[1] Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK;Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London, UK;Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK;Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK;Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London, UK;Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK;Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK;

关键词: DNA methylation;    Oligodendrocytes;    Neurodegeneration;    Myelin;    Epigenetics;    Human brain;   

DOI  :  10.1186/s40478-023-01607-9

 received in 2023-05-03, accepted in 2023-06-20,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

42004_2023_911_Article_IEq15.gif

Fig. 7

40538_2023_419_Article_IEq1.gif

Fig. 3

Fig. 1