{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:13:02Z","timestamp":1770819182342,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson\u2019s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of \u03b1-synuclein (\u03b1syn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP+)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing \u03b1syn inclusions as well as their size and subcellular localization in a yeast model of \u03b1syn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates \u03b1syn aggregation, supporting the idea that diets rich in this compound may prove beneficial.<\/jats:p>","DOI":"10.3390\/molecules26113353","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T10:38:39Z","timestamp":1622630319000},"page":"3353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Small Molecule Fisetin Modulates Alpha\u2013Synuclein Aggregation"],"prefix":"10.3390","volume":"26","author":[{"given":"Rita","family":"Rosado-Ramos","sequence":"first","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"},{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"}]},{"given":"Joana","family":"Godinho-Pereira","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Daniela","family":"Marques","sequence":"additional","affiliation":[{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4639-6883","authenticated-orcid":false,"given":"In\u00eas","family":"Figueira","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1679-1727","authenticated-orcid":false,"given":"Tiago","family":"Fleming Outeiro","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"},{"name":"Max Planck Institute for Experimental Medicine, 37075 G\u00f6ttingen, Germany"},{"name":"Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK"},{"name":"Scientific Employee with a Honorary Contract at Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), 37075 G\u00f6ttingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0552-8480","authenticated-orcid":false,"given":"Regina","family":"Menezes","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"},{"name":"CBIOS\u2014Universidade Lus\u00f3fona\u2019s Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-1924","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Nunes dos Santos","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Apartado 12, 2781-901 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"},{"name":"CEDOC, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, Campo dos M\u00e1rtires da P\u00e1tria, 130, 1169-056 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","article-title":"Epidemiology of Parkinson\u2019s Disease","volume":"5","author":"Breteler","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nm.4269","article-title":"\u03b1-Synuclein Toxicity in Neurodegeneration: Mechanism and Therapeutic Strategies","volume":"23","author":"Wong","year":"2017","journal-title":"Nat. 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