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The emerging nexus of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons.

Abstract：

:The variable patterns of DNA methylation in mammals have been linked to a number of physiological processes, including normal embryonic development and disease pathogenesis. Active removal of DNA methylation, which potentially regulates neuronal gene expression both globally and gene specifically, has been recently implicated in neuronal plasticity, learning and memory processes. Model pathways of active DNA demethylation involve ten-eleven translocation (TET) methylcytosine dioxygenases that are dependent on oxidative metabolites. In addition, reactive oxygen species (ROS) and oxidizing agents generate oxidative modifications of DNA bases that can be removed by base excision repair proteins. These potentially link the two processes of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons. We review the current biochemical understanding of the DNA demethylation process and discuss its potential interaction with oxidative metabolism. We then summarise the emerging roles of both processes and their interaction in neural plasticity and memory formation and the pathophysiology of neurodegeneration. Finally, possible therapeutic approaches for neurodegenerative diseases are proposed, including reprogramming therapy by global DNA demethylation and mitohormesis therapy for locus-specific DNA demethylation in post-mitotic neurons.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Meng H,Chen G,Gao HM,Song X,Shi Y,Cao L

doi

10.3390/ijms151222604

subject

Has Abstract

pub_date

2014-12-05 00:00:00

pages

22604-25

issue

12

issn

1422-0067

pii

ijms151222604

journal_volume

15

pub_type

杂志文章,评审

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