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The cause of degeneration is not well understood; however, both genetics and environmental factors, such as nutrition, have been implicated in the disease process. Deficiencies in one-carbon metabolism in particular have been associated with increased risk for PD onset and progression, though the precise relationship is unclear. The aim of the present review is to determine the role of one-carbon metabolism and elevated levels of homocysteine in PD onset and pathology and to identify potential mechanisms involved. A search of PubMed, Google Scholar and Web of Science was undertaken to identify relevant human and animal studies. Case\u2013control, prospective cohort studies, meta-analyses and non-randomised trials were included in the present review. The results from human studies indicate that polymorphisms in one-carbon metabolism may increase risk for PD development. There is an unclear role for dietary B-vitamin intake on PD onset and progression. However, dietary supplementation with B-vitamins may be beneficial for PD-affected individuals, particularly those on<jats:sc>l<\/jats:sc>-DOPA (levodopa or<jats:sc>l<\/jats:sc>-3,4-dihydroxyphenylalanine) treatment. Additionally, one-carbon metabolism generates methyl groups, and methylation capacity in PD-affected individuals is reduced. This reduced capacity has an impact on expression of disease-specific genes that may be involved in PD progression. During B-vitamin deficiency, animal studies report increased vulnerability of DA cells through increased oxidative stress and altered methylation. Nutrition, especially folates and related B-vitamins, may contribute to the onset and progression of PD by making the brain more vulnerable to damage; however, further investigation is required.<\/jats:p>","DOI":"10.1017\/s0954422419000106","type":"journal-article","created":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T04:23:42Z","timestamp":1563164622000},"page":"218-230","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":40,"title":["The role of one-carbon metabolism and homocysteine in Parkinson\u2019s disease onset, pathology and mechanisms"],"prefix":"10.1017","volume":"32","author":[{"given":"Lauren K.","family":"Murray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3557-7307","authenticated-orcid":false,"given":"Nafisa M.","family":"Jadavji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2019,7,15]]},"reference":[{"key":"S0954422419000106_ref96","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.034"},{"key":"S0954422419000106_ref65","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(00)00557-9"},{"key":"S0954422419000106_ref48","first-page":"45","article-title":"Nutritional status in patients with Parkinson\u2019s disease at a third-level hospital in Northeastern Mexico","volume":"19","author":"L\u00f3pez-Botello","year":"2017","journal-title":"Med Univ"},{"key":"S0954422419000106_ref91","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5923"},{"key":"S0954422419000106_ref28","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021299117308"},{"key":"S0954422419000106_ref85","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.05.011"},{"key":"S0954422419000106_ref73","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(71)90030-4"},{"key":"S0954422419000106_ref94","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.05.048"},{"key":"S0954422419000106_ref12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2008.01869.x"},{"key":"S0954422419000106_ref45","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-014-2052-6"},{"key":"S0954422419000106_ref81","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(01)93580-0"},{"key":"S0954422419000106_ref80","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-2863(97)00110-1"},{"key":"S0954422419000106_ref84","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199702000-00007"},{"key":"S0954422419000106_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.02.001"},{"key":"S0954422419000106_ref37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197001012820112"},{"key":"S0954422419000106_ref40","doi-asserted-by":"publisher","DOI":"10.1007\/s004150050292"},{"key":"S0954422419000106_ref89","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01752.2002"},{"key":"S0954422419000106_ref72","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20261"},{"key":"S0954422419000106_ref41","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)01660-8"},{"key":"S0954422419000106_ref52","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh213"},{"key":"S0954422419000106_ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-011-9581-6"},{"key":"S0954422419000106_ref17","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00036"},{"key":"S0954422419000106_ref19","doi-asserted-by":"publisher","DOI":"10.3390\/nu3030370"},{"key":"S0954422419000106_ref39","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0106-5"},{"key":"S0954422419000106_ref6","unstructured":"6. 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