DNA cytosine methylation is a principal epigenetic mechanism underlying transcription during development and aging. Growing evidence suggests that DNA methylation plays a critical role in brain function, including neurogenesis, neuronal differentiation, synaptogenesis, learning, and memory. However, the mechanisms underlying aberrant DNA methylation in neurodegenerative diseases remain unclear. In this review, we provide an overview of the contribution of 5-methycytosine (5mC) and 5-hydroxylcytosine (5hmC) to brain development and aging, with a focus on the roles of dynamic 5mC and 5hmC changes in the pathogenesis of neurodegenerative diseases, particularly Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Identification of aberrant DNA methylation sites could provide potential candidates for epigenetic-based diagnostic and therapeutic strategies for neurodegenerative diseases.
Keywords: DNA methylation; aging; development; neurodegenerative diseases; neurogenesis; transcriptional regulation.