{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:43:52Z","timestamp":1789393432598,"version":"build-2803163510"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"870","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:p>\n            Chronic exposure to manganese (Mn) induces manganism and has been widely implicated as a contributing environmental factor to Parkinson\u2019s disease (PD), featuring notable overlaps between the two in motor symptoms and clinical hallmarks. Here, we developed an adult\n            <jats:italic>Drosophila<\/jats:italic>\n            model of Mn toxicity that recapitulated key parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosomes and mitochondria. Metabolomics analysis of the brain and body tissues of these flies at an early stage of toxicity identified systemic changes in the metabolism of biotin (also known as vitamin B\n            <jats:sub>7<\/jats:sub>\n            ) in Mn-treated groups. Biotinidase-deficient flies showed exacerbated Mn-induced neurotoxicity, parkinsonism, and mitochondrial dysfunction. Supplementing the diet of wild-type flies with biotin ameliorated the pathological phenotypes of concurrent exposure to Mn. Biotin supplementation also ameliorated the pathological phenotypes of three standard fly models of PD. Furthermore, supplementing the culture media of human induced stem cells (iPSCs) differentiated midbrain dopaminergic neurons with biotin protected against Mn-induced mitochondrial dysregulation, cytotoxicity, and neuronal loss. Last, analysis of the expression of genes encoding biotin-related proteins in patients with PD revealed increased amounts of biotin transporters in the substantia nigra compared with healthy controls, suggesting a potential role of altered biotin metabolism in PD. Together, our findings identified changes in biotin metabolism as underlying Mn neurotoxicity and parkinsonian pathology in flies, for which dietary biotin supplementation was preventative.\n          <\/jats:p>","DOI":"10.1126\/scisignal.adn9868","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T18:58:43Z","timestamp":1737485923000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":18,"title":["Biotin mitigates the development of manganese-induced, Parkinson\u2019s disease\u2013related neurotoxicity in\n            <i>Drosophila<\/i>\n            and human neurons"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-0897","authenticated-orcid":true,"given":"Yunjia","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5962-4246","authenticated-orcid":true,"given":"Pablo","family":"Reina-Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gali","family":"Maor","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8984-1284","authenticated-orcid":true,"given":"Gary W.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7384-0508","authenticated-orcid":true,"given":"Souvarish","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA."},{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"United Nations Department of Economic and Social Affairs \u201cWorld Social Report 2023: Leaving No One Behind in an Ageing World\u201d (United Nations 2023)."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.4152"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30230-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu247"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aau4543"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aat9900"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00654"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-229002"},{"key":"e_1_3_2_11_2","first-page":"1239","article-title":"Drosophila melanogaster\u2014An embryonic model for studying behavioral and biochemical effects of manganese exposure","volume":"13","author":"Ternes A. 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