{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:54:42Z","timestamp":1760784882116,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre Poland","award":["UMO-2015\/19\/B\/NZ3\/01515"],"award-info":[{"award-number":["UMO-2015\/19\/B\/NZ3\/01515"]}]},{"name":"COST Action PROTEOSTASIS (BM1307), supported by COST (European Cooperation in Science and Technology)","award":["BM1307"],"award-info":[{"award-number":["BM1307"]}]},{"name":"iNOVA4Health","award":["UID\/Multi\/04462\/2019"],"award-info":[{"award-number":["UID\/Multi\/04462\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Several rare neurodegenerative diseases, including chorea acanthocytosis, are caused by mutations in the VPS13A\u2013D genes. Only symptomatic treatments for these diseases are available. Saccharomyces cerevisiae contains a unique VPS13 gene and the yeast vps13\u0394 mutant has been proven as a suitable model for drug tests. A library of drugs and an in-house library of natural compounds and their derivatives were screened for molecules preventing the growth defect of vps13\u0394 cells on medium with sodium dodecyl sulfate (SDS). Seven polyphenols, including the iron-binding flavone luteolin, were identified. The structure\u2013activity relationship and molecular mechanisms underlying the action of luteolin were characterized. The FET4 gene, which encodes an iron transporter, was found to be a multicopy suppressor of vps13\u0394, pointing out the importance of iron in response to SDS stress. The growth defect of vps13\u0394 in SDS-supplemented medium was also alleviated by the addition of iron salts. Suppression did not involve cell antioxidant responses, as chemical antioxidants were not active. Our findings support that luteolin and iron may target the same cellular process, possibly the synthesis of sphingolipids. Unveiling the mechanisms of action of chemical and genetic suppressors of vps13\u0394 may help to better understand VPS13A\u2013D-dependent pathogenesis and to develop novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/genes11070828","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T03:23:16Z","timestamp":1595388196000},"page":"828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Flavonoids as Potential Drugs for VPS13-Dependent Rare Neurodegenerative Diseases"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-4069","authenticated-orcid":false,"given":"Piotr","family":"Soczewka","sequence":"first","affiliation":[{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106 Warsaw, Poland"}]},{"given":"Krzysztof","family":"Flis","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106 Warsaw, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2290-5375","authenticated-orcid":false,"given":"D\u00e9borah","family":"Tribouillard-Tanvier","sequence":"additional","affiliation":[{"name":"CNRS, Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires, Bordeaux University, CEDEX, 33077 Bordeaux, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale INSERM, 33077 Bordeaux, France"}]},{"given":"Jean-Paul","family":"di Rago","sequence":"additional","affiliation":[{"name":"CNRS, Institut de Biochimie et G\u00e9n\u00e9tique Cellulaires, Bordeaux University, CEDEX, 33077 Bordeaux, France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-1924","authenticated-orcid":false,"given":"Cl\u00e1udia N.","family":"Santos","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. Rep\u00fablica, Qta. do Marqu\u00eas, 2780-157 Oeiras, Portugal"},{"name":"CEDOC\u2014Chronic Diseases Research Center, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Rua C\u00e2mara Pestana n\u00b0 6, 6-A Edif\u00edcio CEDOC II, 1150-082 Lisboa, Portugal"}]},{"given":"Regina","family":"Menezes","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. Rep\u00fablica, Qta. do Marqu\u00eas, 2780-157 Oeiras, Portugal"},{"name":"CEDOC\u2014Chronic Diseases Research Center, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Rua C\u00e2mara Pestana n\u00b0 6, 6-A Edif\u00edcio CEDOC II, 1150-082 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0168-7882","authenticated-orcid":false,"given":"Joanna","family":"Kaminska","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106 Warsaw, Poland"}]},{"given":"Teresa","family":"Zoladek","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106 Warsaw, Poland"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.ijbiomac.2017.07.116","article-title":"A review on protein misfolding, aggregation and strategies to prevent related ailments","volume":"105","author":"Shamsi","year":"2017","journal-title":"Int. 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