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Previous studies from our group identified the presence of anti-inflammatory and antioxidant compounds in leaves derived from the Chilean berry <jats:italic>Ugni molinae<\/jats:italic> (murtilla), in addition to show a potent anti-aggregation activity in models of Alzheimer\u00b4s disease. However, possible beneficial effects of berry extracts of murtilla was not investigated. Here we evaluated the efficacy of fruit extracts from different genotypes of Chilean-native <jats:italic>U<\/jats:italic>. <jats:italic>molinae<\/jats:italic> on reducing protein aggregation using cellular models of Huntington\u00b4s disease and assess the correlation with their chemical composition. Berry extraction was performed by exhaustive maceration with increasing-polarity solvents. An unbiased automatic microscopy platform was used for cytotoxicity and protein aggregation studies in HEK293 cells using polyglutamine-EGFP fusion proteins, followed by secondary validation using biochemical assays. Phenolic-rich extracts from murtilla berries of the 19\u20131 genotype (ETE 19\u20131) significantly reduced polyglutamine peptide aggregation levels, correlating with the modulation in the expression levels of autophagy-related proteins. Using LC-MS and molecular network analysis we correlated the presence of flavonoids, phenolic acids, and ellagitannins with the protective effects of ETE 19\u20131 effects on protein aggregation. Overall, our results indicate the presence of bioactive components in ethanolic extracts from <jats:italic>U<\/jats:italic>. <jats:italic>molinae<\/jats:italic> berries that reduce the load of protein aggregates in living cells.<\/jats:p>","DOI":"10.1371\/journal.pone.0254834","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T18:46:27Z","timestamp":1627584387000},"page":"e0254834","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington\u2019s disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7180-8547","authenticated-orcid":true,"given":"Rodrigo","family":"P\u00e9rez-Arancibia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Ordo\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Rivas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pih\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Sagredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulises","family":"Ahumada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Barriga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivette","family":"Seguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"C\u00e1rdenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene L.","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Hetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Delporte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"issue":"10","key":"pone.0254834.ref001","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s41593-018-0235-9","article-title":"Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases","volume":"21","author":"C Soto","year":"2018","journal-title":"Nat Neurosci"},{"issue":"12","key":"pone.0254834.ref002","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1038\/nm.4001","article-title":"Proteostasis and aging","volume":"21","author":"S Kaushik","year":"2015","journal-title":"Nat Med"},{"issue":"6","key":"pone.0254834.ref003","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.cell.2021.02.007","article-title":"Adapting the proteostasis capacity to sustain brain healthspan","volume":"184","author":"C. 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