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

被引:6
|
作者
Fodder, Katherine [1 ,2 ]
de Silva, Rohan [3 ,4 ]
Warner, Thomas T. [1 ,3 ,4 ]
Bettencourt, Conceicao [1 ,2 ]
机构
[1] UCL Queen Sq Inst Neurol, Queen Sq Brain Bank Neurol Disorders, London, England
[2] UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, London, England
[3] UCL Queen Sq Inst Neurol, Dept Clin & Movement Neurosci, London, England
[4] UCL Queen Sq Inst Neurol, Reta Lila Weston Inst, London, England
基金
英国医学研究理事会;
关键词
DNA methylation; Oligodendrocytes; Neurodegeneration; Myelin; Epigenetics; Human brain; PROGRESSIVE SUPRANUCLEAR PALSY; MULTIPLE SYSTEM ATROPHY; ALZHEIMERS-DISEASE; GENE-EXPRESSION; CELL-DEATH; MYELIN; BRAIN; RISK; DEGENERATION; ASSOCIATION;
D O I
10.1186/s40478-023-01607-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
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 & beta;-amyloid plaques in Alzheimer's disease (AD), inclusions of hyperphosphorylated microtubule-binding tau in AD and other tauopathies, or inclusions containing & alpha;-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.
引用
收藏
页数:15
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