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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\u2019s disease (AD), Parkinson\u2019s disease (PD), and Huntington\u2019s disease (HD). Identification of aberrant DNA methylation sites could provide potential candidates for epigenetic-based diagnostic and therapeutic strategies for neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/biology12020152","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:04:35Z","timestamp":1674093875000},"page":"152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Dynamic Regulation of DNA Methylation and Brain Functions"],"prefix":"10.3390","volume":"12","author":[{"given":"Jiaxiang","family":"Xie","sequence":"first","affiliation":[{"name":"Guangdong Key Laboratory of Non-Human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leijie","family":"Xie","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Non-Human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixian","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Non-Human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Non-Human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-0762","authenticated-orcid":false,"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Non-Human Primate Research, Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1126\/science.187.4173.226","article-title":"DNA modification mechanisms and gene activity during development","volume":"187","author":"Holliday","year":"1975","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35049533","article-title":"DNA methylation in health and disease","volume":"1","author":"Robertson","year":"2000","journal-title":"Nat. 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