{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:03:32Z","timestamp":1785301412969,"version":"3.55.0"},"reference-count":144,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Excellence Strategy of the Federal Government and the L\u00e4nder","award":["SFASIA002"],"award-info":[{"award-number":["SFASIA002"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZI-1224\/20-1"],"award-info":[{"award-number":["ZI-1224\/20-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["ZI-1224\/19-1"],"award-info":[{"award-number":["ZI-1224\/19-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["368482240\/GRK2416"],"award-info":[{"award-number":["368482240\/GRK2416"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    DNA methyltransferase 1 (DNMT1) has classically been viewed as the canonical maintenance methyltransferase, yet accumulating evidence positions it as a multifaceted hub that integrates environmental, hormonal, and metabolic signals with chromatin regulation in the developing and adult brain. This review highlights DNMT1 as an environmentally responsive epigenetic sensor across the lifespan. We examine how psychosocial stress, early-life adversity, inflammation, nutritional and microbiome-derived metabolites, and environmental toxicants modulate DNMT1 expression, subcellular localization, and post-translational modifications, thereby reshaping DNA methylation landscapes in neurons and glia. We further discuss how sex hormone signaling, particularly estrogen receptor alpha\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (ER\u03b1)-DNMT1 feedback loops, introduces sex-specific dimensions to epigenetic responsiveness, and how lncRNAs serve as intermediaries linking environmental cues to targeted DNMT1 recruitment at specific genomic loci. Building on this framework, we review how DNMT1 dysregulation contributes to neurodevelopmental and neuropsychiatric disorders\u2014including schizophrenia, autism spectrum disorder, and depression\u2014and to neurodegenerative conditions such as Parkinson\u2019s disease, Alzheimer\u2019s disease, amyotrophic lateral sclerosis, and DNMT1-associated monogenic neurodegenerative disorders. By positioning DNMT1 as a molecular interface between genetic predisposition, environmental exposure, and circuit-level vulnerability, this review highlights the need for integrated, sex-stratified, and longitudinal approaches to understanding epigenetic risk in neurological disease.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1883887","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:45:10Z","timestamp":1785300310000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["DNMT1 as an environmental sensor: epigenetic pathways linking environmental exposures, sex hormone signaling, and vulnerability to neurodevelopmental and neurodegenerative diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Katharina","family":"V\u00f6hringer","sequence":"first","affiliation":[{"name":"Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University","place":["Aachen, Germany"]},{"name":"Research Training Group 2416 MultiSenses \u2013 MultiScales, RWTH Aachen University","place":["Aachen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena Sophie","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University","place":["Aachen, Germany"]},{"name":"Research Training Group 2416 MultiSenses \u2013 MultiScales, RWTH Aachen University","place":["Aachen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can Bora","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University","place":["Aachen, Germany"]},{"name":"Research Training Group 2416 MultiSenses \u2013 MultiScales, RWTH Aachen University","place":["Aachen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Zimmer-Bensch","sequence":"additional","affiliation":[{"name":"Division of Neuroepigenetics, Institute of Zoology (Biology 2), RWTH Aachen University","place":["Aachen, Germany"]},{"name":"Research Training Group 2416 MultiSenses \u2013 MultiScales, RWTH Aachen University","place":["Aachen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.neuron.2019.07.009","article-title":"Development and Arealization of the cerebral cortex","volume":"103","author":"Cadwell","year":"2019","journal-title":"Neuron"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/nrn3586","article-title":"Molecular logic of neocortical projection neuron specification, development and 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