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Small molecules able to target key pathological processes in PD have emerged as interesting options for modifying disease progression. We have previously shown that a (poly)phenol-enriched fraction (PEF) of <jats:italic>Corema album<\/jats:italic> L. leaf extract modulates central events in PD pathogenesis, namely \u03b1-synuclein (\u03b1Syn) toxicity, aggregation and clearance. PEF was now subjected to a bio-guided fractionation with the aim of identifying the critical bioactive compound. We identified genipin, an iridoid, which relieves \u03b1Syn toxicity and aggregation. Furthermore, genipin promotes metabolic alterations and modulates lipid storage and endocytosis. Importantly, genipin was able to prevent the motor deficits caused by the overexpression of \u03b1Syn in a <jats:italic>Drosophila melanogaster<\/jats:italic> model of PD. These findings widens the possibility for the exploitation of genipin for PD therapeutics.<\/jats:p>","DOI":"10.1038\/s41467-023-37561-2","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T12:05:58Z","timestamp":1680782758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage"],"prefix":"10.1038","volume":"14","author":[{"given":"Rita","family":"Rosado-Ramos","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-1618","authenticated-orcid":false,"given":"Gon\u00e7alo M.","family":"Po\u00e7as","sequence":"additional","affiliation":[]},{"given":"Daniela","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Alexandre","family":"Foito","sequence":"additional","affiliation":[]},{"given":"David","family":"M. 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