{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T04:48:39Z","timestamp":1771735719226,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Epigenetic factors including DNA methylation contribute to specific patterns of gene expression. Gene\u2013environment interactions can change the methylation status in the brain, and accumulation of these epigenetic changes over a lifespan may be co-responsible for a neurodegenerative disease like Parkinson\u2019s disease, which that is characterised by a late onset in life. Aims: To determine epigenetic modifications in the brains of Parkinson\u2019s disease patients. Patients and Methods: DNA methylation patterns were compared in the cortex tissue of 14 male PD patients and 10 male healthy individuals using the Illumina Methylation 450 K chip. Subsequently, DNA methylation of candidate genes was evaluated using bisulphite pyrosequencing, and DNA methylation of cytochrome P450 2E1 (CYP2E1) was characterized in DNA from blood mononuclear cells (259 PD patients and 182 healthy controls) and skin fibroblasts (10 PD patients and 5 healthy controls). Protein levels of CYP2E1 were analysed using Western blot in human cortex and knock-out mice brain samples. Results: We found 35 hypomethylated and 22 hypermethylated genes with a methylation M-value difference &gt;0.5. Decreased methylation of cytochrome P450 2E1 (CYP2E1) was associated with increased protein levels in PD brains, but in peripheral tissues, i.e., in blood cells and skin fibroblasts, DNA methylation of CYP2E1 was unchanged. In CYP2E1 knock-out mice brain alpha-synuclein (SNCA) protein levels were down-regulated compared to wild-type mice, whereas treatment with trichloroethylene (TCE) up-regulated CYP2E1 protein in a dose-dependent manner in cultured cells. We further identified an interconnected group of genes associated with oxidative stress, such as Methionine sulfoxide reductase A (MSRA) and tumour protein 73 (TP73) in the brain, which again were not paralleled in other tissues and appeared to indicate brain-specific changes. Conclusions: Our study revealed surprisingly few dysmethylated genes in a brain region less affected in PD. We confirmed hypomethylation of CYP2E1.<\/jats:p>","DOI":"10.3390\/life12040502","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:41:30Z","timestamp":1648590090000},"page":"502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Epigenome-Wide Analysis of DNA Methylation in Parkinson\u2019s Disease Cortex"],"prefix":"10.3390","volume":"12","author":[{"given":"Oliver","family":"Kaut","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Bonn, 53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Bonn, 53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Stahl","sequence":"additional","affiliation":[{"name":"DZNE (Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen), 53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5328-1243","authenticated-orcid":false,"given":"Holger","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[{"name":"Algorithmic Bioinformatics for B-IT, University of Bonn, 53113 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Life & Brain Center, Institute for Human Genetics, Department of Genomics, University of Bonn, 53113 Bonn, Germany"},{"name":"Human Genetics Research Group, Department of Biomedicine, University of Basel, 4001 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-0790","authenticated-orcid":false,"given":"Ullrich","family":"W\u00fcllner","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Bonn, 53105 Bonn, Germany"},{"name":"DZNE (Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen), 53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/S1474-4422(09)70262-5","article-title":"Epigenetic mechanisms in neurological diseases: Genes, syndromes, and therapies","volume":"8","author":"Urdinguio","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrg2341","article-title":"DNA methylation landscapes: Provocative insights from epigenomics","volume":"9","author":"Suzuki","year":"2008","journal-title":"Nat. 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