{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:17:11Z","timestamp":1790846231509,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is the second most common neurodegenerative disorder, characterized by the preferential loss of dopaminergic neurons and by the accumulation of intracellular inclusions mainly composed of \u03b1-synuclein (\u03b1-Syn). While the etiopathogenesis of the disorder is still elusive, recent experimental evidence supports the involvement of ferroptosis, an iron-dependent cell death pathway, in the pathogenesis of PD. In the present work, using different ferroptosis inducers and inhibitors, we evaluated, in vivo, the involvement of iron in the \u03b1-Syn-mediated toxicity. Using a Drosophila melanogaster model of PD based on the selective over-expression of \u03b1-Syn within dopaminergic neurons, we demonstrated that the over-expression of \u03b1-Syn promotes the accumulation of protein aggregates, which is accompanied by dopaminergic neurodegeneration, locomotor impairment, and lifespan reduction. These pathological phenotypes were further exacerbated by reduced intracellular levels of glutathione or increased concentrations of iron. Coherently, both the use of an iron chelator and the presence of the antioxidant compound N-acetylcysteine exerted protective effects. Overall, our results support the involvement of ferroptosis in the \u03b1-Syn-mediated toxicity.<\/jats:p>","DOI":"10.3390\/antiox12020261","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T01:59:03Z","timestamp":1674525543000},"page":"261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["\u03b1-Synuclein Toxicity in Drosophila melanogaster Is Enhanced by the Presence of Iron: Implications for Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9833-6498","authenticated-orcid":false,"given":"Francesco","family":"Agostini","sequence":"first","affiliation":[{"name":"Department of Biology, University of Padova, Via Ugo Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7927-9208","authenticated-orcid":false,"given":"Luigi","family":"Bubacco","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, Via Ugo Bassi 58\/B, 35131 Padova, Italy"},{"name":"Study Center for Neurodegeneration (CESNE), 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasanka","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Central Research Laboratory, Maharishi Markandeshwar Institute of Medical Sciences and Research, Maharishi Markandeshwar University (Deemed to Be), Mullana, Ambala 133207, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3968-8418","authenticated-orcid":false,"given":"Marco","family":"Bisaglia","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, Via Ugo Bassi 58\/B, 35131 Padova, Italy"},{"name":"Study Center for Neurodegeneration (CESNE), 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104782","DOI":"10.1016\/j.nbd.2020.104782","article-title":"Genetics of Parkinson\u2019s Disease: An Introspection of Its Journey towards Precision Medicine","volume":"137","author":"Kim","year":"2020","journal-title":"Neurobiol. 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