CtBP Neuroprotective Role in Toxin-Based Parkinson’s Disease Models
Autor(a) principal: | |
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Data de Publicação: | 2023 |
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/10362/152170 |
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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7160 |
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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 |
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/10362/152170 |
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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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