Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases

Detalhes bibliográficos
Autor(a) principal: Soczewka, Piotr
Data de Publicação: 2020
Outros Autores: Flis, Krzysztof, Tribouillard-Tanvier, Déborah, Di Rago, Jean Paul, Santos, Cláudia N., Menezes, Regina, Kaminska, Joanna, Zoladek, Teresa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/147539
Resumo: Funding: This research was funded by National Science Centre Poland, grant number UMO-2015/19/B/NZ3/01515 to T.Z., the APC was funded by the Institute of Biochemistry and Biophysics Polish Academy of Sciences and the Short Term Scientific Mission of K.F. in R.M. laboratory was funded by COST Action PROTEOSTASIS (BM1307), supported by COST (European Cooperation in Science and Technology). We acknowledge iNOVA4Health—UID/Multi/04462/2019, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. Funding from the INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC) is gratefully acknowledged. This study was also supported by FCT via PTDC/BIA-MOL31104/2017 to R.M.
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spelling Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseasesCsg2∆Drug repurposingFET4 geneIronLuteolinNeurodegenerative diseasesSphingolipid biosynthesisTolcaponeVPS13 genesYeast modelGeneticsGenetics(clinical)Funding: This research was funded by National Science Centre Poland, grant number UMO-2015/19/B/NZ3/01515 to T.Z., the APC was funded by the Institute of Biochemistry and Biophysics Polish Academy of Sciences and the Short Term Scientific Mission of K.F. in R.M. laboratory was funded by COST Action PROTEOSTASIS (BM1307), supported by COST (European Cooperation in Science and Technology). We acknowledge iNOVA4Health—UID/Multi/04462/2019, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. Funding from the INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC) is gratefully acknowledged. This study was also supported by FCT via PTDC/BIA-MOL31104/2017 to R.M.Several rare neurodegenerative diseases, including chorea acanthocytosis, are caused by mutations in the VPS13A–D genes. Only symptomatic treatments for these diseases are available. Saccharomyces cerevisiae contains a unique VPS13 gene and the yeast vps13∆ 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∆ cells on medium with sodium dodecyl sulfate (SDS). Seven polyphenols, including the iron-binding flavone luteolin, were identified. The structure–activity 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∆, pointing out the importance of iron in response to SDS stress. The growth defect of vps13∆ 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∆ may help to better understand VPS13A–D-dependent pathogenesis and to develop novel therapeutic strategies.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNSoczewka, PiotrFlis, KrzysztofTribouillard-Tanvier, DéborahDi Rago, Jean PaulSantos, Cláudia N.Menezes, ReginaKaminska, JoannaZoladek, Teresa2023-01-13T22:13:39Z2020-072020-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article17application/pdfhttp://hdl.handle.net/10362/147539eng0920-8569PURE: 19797405https://doi.org/10.3390/genes11070828info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:28:44Zoai:run.unl.pt:10362/147539Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:52:59.206589Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
title Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
spellingShingle Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
Soczewka, Piotr
Csg2∆
Drug repurposing
FET4 gene
Iron
Luteolin
Neurodegenerative diseases
Sphingolipid biosynthesis
Tolcapone
VPS13 genes
Yeast model
Genetics
Genetics(clinical)
title_short Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
title_full Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
title_fullStr Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
title_full_unstemmed Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
title_sort Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
author Soczewka, Piotr
author_facet Soczewka, Piotr
Flis, Krzysztof
Tribouillard-Tanvier, Déborah
Di Rago, Jean Paul
Santos, Cláudia N.
Menezes, Regina
Kaminska, Joanna
Zoladek, Teresa
author_role author
author2 Flis, Krzysztof
Tribouillard-Tanvier, Déborah
Di Rago, Jean Paul
Santos, Cláudia N.
Menezes, Regina
Kaminska, Joanna
Zoladek, Teresa
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Soczewka, Piotr
Flis, Krzysztof
Tribouillard-Tanvier, Déborah
Di Rago, Jean Paul
Santos, Cláudia N.
Menezes, Regina
Kaminska, Joanna
Zoladek, Teresa
dc.subject.por.fl_str_mv Csg2∆
Drug repurposing
FET4 gene
Iron
Luteolin
Neurodegenerative diseases
Sphingolipid biosynthesis
Tolcapone
VPS13 genes
Yeast model
Genetics
Genetics(clinical)
topic Csg2∆
Drug repurposing
FET4 gene
Iron
Luteolin
Neurodegenerative diseases
Sphingolipid biosynthesis
Tolcapone
VPS13 genes
Yeast model
Genetics
Genetics(clinical)
description Funding: This research was funded by National Science Centre Poland, grant number UMO-2015/19/B/NZ3/01515 to T.Z., the APC was funded by the Institute of Biochemistry and Biophysics Polish Academy of Sciences and the Short Term Scientific Mission of K.F. in R.M. laboratory was funded by COST Action PROTEOSTASIS (BM1307), supported by COST (European Cooperation in Science and Technology). We acknowledge iNOVA4Health—UID/Multi/04462/2019, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. Funding from the INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC) is gratefully acknowledged. This study was also supported by FCT via PTDC/BIA-MOL31104/2017 to R.M.
publishDate 2020
dc.date.none.fl_str_mv 2020-07
2020-07-01T00:00:00Z
2023-01-13T22:13:39Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/147539
url http://hdl.handle.net/10362/147539
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0920-8569
PURE: 19797405
https://doi.org/10.3390/genes11070828
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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