CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models

Detalhes bibliográficos
Autor(a) principal: Saraiva, Cláudia
Data de Publicação: 2023
Outros Autores: Lopes-Nunes, Jéssica, Esteves, Marta, Santos, Tiago, Vale, Ana, Cristóvão, Ana Clara, Ferreira, Raquel, Bernardino, Liliana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/152170
Resumo: Funding Information: Open access funding provided by FCT|FCCN (b-on). This work was supported by “Programa Operacional do Centro, Centro 2020” through the funding of the ICON project (Interdisciplinary Challenges On Neurodegeneration; CENTRO-01–0145-FEDER-000013), and by the following national funds: Foundation for Science and Technology (doctoral grant SFRH/BD/121822/2016), UBI-Santander/Totta (BID/ICI-FCS/CICS/Santander Universidades-UBI/2017) and the PPBI-Portuguese Platform of BioImaging: POCI-01–0145-FEDER-022122. Publisher Copyright: © 2023, The Author(s).
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spelling CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease ModelsFrom Expression Pattern to Dopaminergic SurvivalAgingC-terminal binding proteinsDopaminergic survivalNeuroprotectionParkinson’s diseaseNeurologyCellular and Molecular NeuroscienceFunding Information: Open access funding provided by FCT|FCCN (b-on). This work was supported by “Programa Operacional do Centro, Centro 2020” through the funding of the ICON project (Interdisciplinary Challenges On Neurodegeneration; CENTRO-01–0145-FEDER-000013), and by the following national funds: Foundation for Science and Technology (doctoral grant SFRH/BD/121822/2016), UBI-Santander/Totta (BID/ICI-FCS/CICS/Santander Universidades-UBI/2017) and the PPBI-Portuguese Platform of BioImaging: POCI-01–0145-FEDER-022122. Publisher Copyright: © 2023, The Author(s).C-terminal binding proteins (CtBP) are transcriptional co-repressors regulating gene expression. CtBP promote neuronal survival through repression of pro-apoptotic genes, and may represent relevant targets for neurodegenerative disorders, such as Parkinson’s disease (PD). Nevertheless, evidence of the role of CtBP1 and CtBP2 in neurodegeneration are scarce. Herein, we showed that CtBP1 and CtBP2 are expressed in neurons, dopaminergic neurons, astrocytes, and microglia in the substantia nigra (SN) and striatum of adult mice. Old mice showed a lower expression of CtBP1 in the SN and higher expression of CtPB2 in the SN and striatum compared with adult mice. In vivo models for PD (paraquat, MPTP, 6-OHDA) showed increased expression of CtBP1 in the SN and striatum while CtBP2 expression was increased in the striatum of paraquat-treated rats only. Moreover, an increased expression of both CtBP was found in a dopaminergic cell line (N27) exposed to 6-OHDA. In the 6-OHDA PD model, we found a dual effect using an unspecific ligand of CtBP, the 4-methylthio 2-oxobutyric acid (MTOB): higher concentrations (e.g. 2500 µM, 1000 µM) inhibited dopaminergic survival, while at 250 μM it counteracted cell death. In vitro, this latter protective role was absent after the siRNA silencing of CtBP1 or CtBP2. Altogether, this is the first report exploring the cellular and regional expression pattern of CtBP in the nigrostriatal pathway and the neuroprotective role in PD toxin-based models. CtBP could counteract dopaminergic cell death in the 6-OHDA PD model and, therefore, CtBP function and therapeutic potential in PD should be further explored.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNSaraiva, CláudiaLopes-Nunes, JéssicaEsteves, MartaSantos, TiagoVale, AnaCristóvão, Ana ClaraFerreira, RaquelBernardino, Liliana2023-04-26T22:21:02Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/152170eng0893-7648PURE: 59389691https://doi.org/10.1007/s12035-023-03331-winfo: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:RCAAP2024-03-11T05:34:30Zoai:run.unl.pt:10362/152170Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:54:48.823985Repositório 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 CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
From Expression Pattern to Dopaminergic Survival
title CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
spellingShingle CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
Saraiva, Cláudia
Aging
C-terminal binding proteins
Dopaminergic survival
Neuroprotection
Parkinson’s disease
Neurology
Cellular and Molecular Neuroscience
title_short CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
title_full CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
title_fullStr CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
title_full_unstemmed CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
title_sort CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
author Saraiva, Cláudia
author_facet Saraiva, Cláudia
Lopes-Nunes, Jéssica
Esteves, Marta
Santos, Tiago
Vale, Ana
Cristóvão, Ana Clara
Ferreira, Raquel
Bernardino, Liliana
author_role author
author2 Lopes-Nunes, Jéssica
Esteves, Marta
Santos, Tiago
Vale, Ana
Cristóvão, Ana Clara
Ferreira, Raquel
Bernardino, Liliana
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Saraiva, Cláudia
Lopes-Nunes, Jéssica
Esteves, Marta
Santos, Tiago
Vale, Ana
Cristóvão, Ana Clara
Ferreira, Raquel
Bernardino, Liliana
dc.subject.por.fl_str_mv Aging
C-terminal binding proteins
Dopaminergic survival
Neuroprotection
Parkinson’s disease
Neurology
Cellular and Molecular Neuroscience
topic Aging
C-terminal binding proteins
Dopaminergic survival
Neuroprotection
Parkinson’s disease
Neurology
Cellular and Molecular Neuroscience
description Funding Information: Open access funding provided by FCT|FCCN (b-on). This work was supported by “Programa Operacional do Centro, Centro 2020” through the funding of the ICON project (Interdisciplinary Challenges On Neurodegeneration; CENTRO-01–0145-FEDER-000013), and by the following national funds: Foundation for Science and Technology (doctoral grant SFRH/BD/121822/2016), UBI-Santander/Totta (BID/ICI-FCS/CICS/Santander Universidades-UBI/2017) and the PPBI-Portuguese Platform of BioImaging: POCI-01–0145-FEDER-022122. Publisher Copyright: © 2023, The Author(s).
publishDate 2023
dc.date.none.fl_str_mv 2023-04-26T22:21:02Z
2023
2023-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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url http://hdl.handle.net/10362/152170
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0893-7648
PURE: 59389691
https://doi.org/10.1007/s12035-023-03331-w
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eu_rights_str_mv openAccess
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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
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