{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:01:54Z","timestamp":1784523714195,"version":"3.55.0"},"reference-count":74,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Italian Ministry for Universities and Research","doi-asserted-by":"crossref","award":["l. 232\/2016, art. 1, commi 314\u2013337"],"award-info":[{"award-number":["l. 232\/2016, art. 1, commi 314\u2013337"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aberrant self-assembly of ataxin-3 (ATX3) into amyloid aggregates is a key pathological event in spinocerebellar ataxia type 3 (SCA3). Bioactive nutraceutical compounds, particularly polyphenols, have emerged as promising candidates for targeting protein aggregation and cellular stress responses associated with neurodegenerative disorders. Here, we investigated cinnamon bud extract as a natural source of neuroprotective molecules, focusing on its total extract (Etot) and two bioactive fractions: a polyphenol-enriched fraction (Fr. B) and a cinnamaldehyde-rich fraction (Fr. C). By integrating biochemical and biophysical techniques, we demonstrate that cinnamon-derived compounds modulate ATX3 aggregation by reducing the formation of \u03b2-sheet-rich amyloid assemblies and promoting the generation of SDS-resistant, soluble, structurally distinct, non-fibrillar species. NMR profiling identified flavonoids, cinnamaldehyde, and cinnamic acid as key ATX3-interacting molecules, supporting their contribution to the anti-amyloidogenic activity of the extract. Moreover, in a Caenorhabditis elegans SCA3 model, Etot and Fr. B improved locomotor defects and enhanced resistance to oxidative and thermal stress, indicating broader cytoprotective effects beyond direct aggregation modulation. Overall, these findings highlight cinnamon bud extract, particularly its polyphenol-rich fraction, as a promising nutraceutical source of bioactive compounds with potential neuroprotective properties and provide a basis for further investigation of nutraceutical strategies targeting polyglutamine-related neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/molecules31142510","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:32:08Z","timestamp":1784514728000},"page":"2510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphenol-Rich Cinnamon Bud Extract Affects Ataxin-3 Aggregation and Ameliorates SCA3 Phenotypes Through a Dual Anti-Amyloidogenic and Antioxidant Mechanism"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5891-0299","authenticated-orcid":false,"given":"Barbara","family":"Sciandrone","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Biosciences BtBs, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pensotti","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences BtBs, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4549-8300","authenticated-orcid":false,"given":"Diletta","family":"Ami","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences BtBs, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Saponara","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Raoul Follereau 3, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9069-8232","authenticated-orcid":false,"given":"Riccardo","family":"Campanile","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Raoul Follereau 3, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0254-8243","authenticated-orcid":false,"given":"Valeria","family":"Cassina","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, Via Raoul Follereau 3, 20854 Vedano al Lambro, Italy"},{"name":"BioNanoMedicine Center NANOMIB, University of Milano-Bicocca, 20854 Vedano al Lambro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1489-272X","authenticated-orcid":false,"given":"Antonino","family":"Natalello","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences BtBs, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5287-1663","authenticated-orcid":false,"given":"Alessandro","family":"Palmioli","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences BtBs, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy"},{"name":"NeuroMI, Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-6262","authenticated-orcid":false,"given":"Cristina","family":"Airoldi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences BtBs, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy"},{"name":"NeuroMI, Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elena","family":"Regonesi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biosciences BtBs, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy"},{"name":"NeuroMI, Milan Center for Neuroscience, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.cell.2022.04.002","article-title":"Nutrition, Longevity and Disease: From Molecular Mechanisms to Interventions","volume":"185","author":"Longo","year":"2022","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Okoro, N.O., Odiba, A.S., Osadebe, P.O., Omeje, E.O., Liao, G., Fang, W., Jin, C., and Wang, B. 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