Review highlights activity-dependent DNA methylation dynamics in the brain, suggesting novel epigenetic targets for treating cognitive decline and Alzheimer's disease.
Key Points
This review synthesizes how activity-dependent DNA methylation and demethylation orchestrate persistent transcriptional programs required for synaptic plasticity, learning, and memory.
Synthesized molecular evidence on canonical cytosine modifications (5mC, 5hmC, 5fC, 5caC) and their modifying enzymes, including DNMTs, TETs, and TDG.
Evaluated emerging literature on non-canonical modifications (6mA and 4mC) alongside recent advances in high-resolution brain epigenomic mapping technologies.
Dynamic oxidative turnover of 5-methylcytosine serves as a primary driver of activity-regulated transcription essential for neuronal plasticity and memory consolidation.
Dysregulation of DNA methylation and demethylation networks is directly linked to transcriptional dysfunction and progressive cognitive decline in Alzheimer's disease.
Emerging high-resolution mapping technologies enable locus- and cell-type-specific tracking of epigenetic marks, providing tools to discover targeted cognitive therapeutics.