{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:59:00Z","timestamp":1790996340129,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust Seed Award in Science","doi-asserted-by":"publisher","award":["217561\/Z\/19\/Z"],"award-info":[{"award-number":["217561\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust Seed Award in Science","doi-asserted-by":"publisher","award":["MR\/P022405\/1"],"award-info":[{"award-number":["MR\/P022405\/1"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["217561\/Z\/19\/Z"],"award-info":[{"award-number":["217561\/Z\/19\/Z"]}]},{"name":"Medical Research Council","award":["MR\/P022405\/1"],"award-info":[{"award-number":["MR\/P022405\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a common movement disorder, estimated to affect 4% of individuals by the age of 80. Mutations in the glucocerebrosidase 1 (GBA1) gene represent the most common genetic risk factor for PD, with at least 7\u201310% of non-Ashkenazi PD individuals carrying a GBA1 mutation (PD-GBA1). Although similar to idiopathic PD, the clinical presentation of PD-GBA1 includes a slightly younger age of onset, a higher incidence of neuropsychiatric symptoms, and a tendency to earlier, more prevalent and more significant cognitive impairment. The pathophysiological mechanisms underlying PD-GBA1 are incompletely understood, but, as in idiopathic PD, \u03b1-synuclein accumulation is thought to play a key role. It has been hypothesized that this overexpression of \u03b1-synuclein is caused by epigenetic modifications. In this paper, we analyze DNA methylation levels at 17 CpG sites located within intron 1 and the promoter of the \u03b1-synuclein (SNCA) gene in three different brain regions (frontal cortex, putamen and substantia nigra) in idiopathic PD, PD-GBA1 and elderly non-PD controls. In all three brain regions we find a tendency towards a decrease in DNA methylation within an eight CpG region of intron 1 in both idiopathic PD and PD-GBA1. The trend towards a reduction in DNA methylation was more pronounced in PD-GBA1, with a significant decrease in the frontal cortex. This suggests that PD-GBA1 and idiopathic PD have distinct epigenetic profiles, and highlights the importance of separating idiopathic PD and PD-GBA1 cases. This work also provides initial evidence that different genetic subtypes might exist within PD, each characterized by its own pathological mechanism. This may have important implications for how PD is diagnosed and treated.<\/jats:p>","DOI":"10.3390\/ijms24032687","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:29:03Z","timestamp":1675218543000},"page":"2687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["DNA Methylation of \u03b1-Synuclein Intron 1 Is Significantly Decreased in the Frontal Cortex of Parkinson\u2019s Individuals with GBA1 Mutations"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-2711","authenticated-orcid":false,"given":"Adam R.","family":"Smith","sequence":"first","affiliation":[{"name":"Faculty of Health and Life Sciences, University of Exeter, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Richards","sequence":"additional","affiliation":[{"name":"Living Systems Institute, University of Exeter, Exeter EX4 4QD, UK"},{"name":"Department of Physics and Astronomy, University of Exeter, Exeter EX4 4QD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Lunnon","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences, University of Exeter, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony H. V.","family":"Schapira","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Migdalska-Richards","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences, University of Exeter, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/gim.2012.107","article-title":"Age-specific Parkinson disease risk in GBA mutation carriers: Information for genetic counseling","volume":"15","author":"Rana","year":"2013","journal-title":"Genet. 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