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Multiple studies suggest a potential neuroprotective role for ET. Here, we show in various Parkinson's disease (PD) models that ET is indeed neuroprotective. Firstly, using\n                    <jats:italic>Drosophila<\/jats:italic>\n                    genetic PD models, we demonstrated that ET treatment ameliorates the pathological phenotypes of\n                    <jats:italic>parkin<\/jats:italic>\n                    and\n                    <jats:italic>LRRK2<\/jats:italic>\n                    PD mutant flies. This includes an improvement in their climbing score and the preservation of their dopaminergic neuronal number and mitochondrial integrity. Similarly, we observed the rescue of PD phenotypes by ET in mice treated with the Parkinsonian neurotoxin 6\u2010OHDA. This protective effect of ET is abolished in mice lacking OCTN1. Finally, we found that ET protects human LRRK2\u2010G2019S patient\u2010derived dopaminergic neurons from rotenone\u2010induced neurotoxicity; the action of ET is again OCTN1\u2010dependent. Collectively, our results strongly support a neuroprotective role for ET in PD and suggest that ET may be useful in the prevention and\/or treatment of PD.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70168-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70168","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T06:40:26Z","timestamp":1753252826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ergothioneine Treatment Ameliorates the Pathological Phenotypes of Parkinson's Disease Models"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-9878","authenticated-orcid":false,"given":"Teddy J. 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Y.","family":"Tang","sequence":"additional","affiliation":[{"name":"Neurobiology Programme, Life Sciences Institute, Centre for Life Sciences National University of Singapore  Singapore Singapore"},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate C. L.","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Neurobiology Programme, Life Sciences Institute, Centre for Life Sciences National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline H.","family":"Basil","sequence":"additional","affiliation":[{"name":"National Neuroscience Institute  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey Ching","family":"Choong","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University  Singapore Singapore"},{"name":"National Neuroscience Institute  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson W. 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