Flavonoids as potential drugs for VPS13-dependent rare neurodegenerative diseases
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
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. |
id |
RCAP_276f641fa0929539ead7d2ba8f98ef50 |
---|---|
oai_identifier_str |
oai:run.unl.pt:10362/147539 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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 |
repository.mail.fl_str_mv |
|
_version_ |
1799138120875114496 |