MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10400.1/17388 |
Resumo: | Background: MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs’ sequence and structure required for this mode of action remained largely unresolved. Methods: Using a microarray-based screening approach we analyzed apoptotic cortical neurons of C56BL/6 mice and their supernatant with respect to alterations in miRNA expression/presence. HEK-Blue Toll-like receptor (TLR) 7/8 reporter cells, primary microglia and macrophages derived from human and mouse were employed to test the potential of the identified miRNAs released from apoptotic neurons to serve as signaling molecules for the RNAsensing receptors. Biophysical and bioinformatical approaches, as well as immunoassays and sequential microscopy were used to analyze the interaction between candidate miRNA and TLR. Immunocytochemical and -histochemical analyses of murine CNS cultures and adult mice intrathecally injected with miRNAs, respectively, were performed to evaluate the impact of miRNA-induced TLR activation on neuronal survival and microglial activation. |
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MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegenerationMicroRNA-100-5p e microRNA-298-5p liberados de neurônios corticais apoptóticos são receptor endógeno tipo Toll 7/8 ligantes que contribuem para a neurodegeneraçãoExtracellular microRNAsEndogenous Toll-like receptor ligandsCortical neuronsNeuronal apoptosisMicrogliaNeurodegenerationmiRNA microarrayBackground: MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs’ sequence and structure required for this mode of action remained largely unresolved. Methods: Using a microarray-based screening approach we analyzed apoptotic cortical neurons of C56BL/6 mice and their supernatant with respect to alterations in miRNA expression/presence. HEK-Blue Toll-like receptor (TLR) 7/8 reporter cells, primary microglia and macrophages derived from human and mouse were employed to test the potential of the identified miRNAs released from apoptotic neurons to serve as signaling molecules for the RNAsensing receptors. Biophysical and bioinformatical approaches, as well as immunoassays and sequential microscopy were used to analyze the interaction between candidate miRNA and TLR. Immunocytochemical and -histochemical analyses of murine CNS cultures and adult mice intrathecally injected with miRNAs, respectively, were performed to evaluate the impact of miRNA-induced TLR activation on neuronal survival and microglial activation.BMCSapientiaWallach, ThomasMossmann, Zoé J.Szczepek, MichalWetzel, MaxMachado, RuiRaden, MartinMiladi, MiladKleinau, GunnarKrüger, ChristinaDembny, PaulAdler, DrewZhai, YuanyuanKumbol, VictorDzaye, OmarSchüler, JuttaFutschik, MatthiasBackofen, RolfScheerer, PatrickLehnardt, Seija2021-12-15T10:47:54Z2021-11-272021-11-27T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/17388eng10.1186/s13024-021-00498-51750-1326info: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:RCAAP2023-07-24T10:29:32Zoai:sapientia.ualg.pt:10400.1/17388Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:07:22.503991Repositório 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 |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration MicroRNA-100-5p e microRNA-298-5p liberados de neurônios corticais apoptóticos são receptor endógeno tipo Toll 7/8 ligantes que contribuem para a neurodegeneração |
title |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration |
spellingShingle |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration Wallach, Thomas Extracellular microRNAs Endogenous Toll-like receptor ligands Cortical neurons Neuronal apoptosis Microglia Neurodegeneration miRNA microarray |
title_short |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration |
title_full |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration |
title_fullStr |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration |
title_full_unstemmed |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration |
title_sort |
MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration |
author |
Wallach, Thomas |
author_facet |
Wallach, Thomas Mossmann, Zoé J. Szczepek, Michal Wetzel, Max Machado, Rui Raden, Martin Miladi, Milad Kleinau, Gunnar Krüger, Christina Dembny, Paul Adler, Drew Zhai, Yuanyuan Kumbol, Victor Dzaye, Omar Schüler, Jutta Futschik, Matthias Backofen, Rolf Scheerer, Patrick Lehnardt, Seija |
author_role |
author |
author2 |
Mossmann, Zoé J. Szczepek, Michal Wetzel, Max Machado, Rui Raden, Martin Miladi, Milad Kleinau, Gunnar Krüger, Christina Dembny, Paul Adler, Drew Zhai, Yuanyuan Kumbol, Victor Dzaye, Omar Schüler, Jutta Futschik, Matthias Backofen, Rolf Scheerer, Patrick Lehnardt, Seija |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Wallach, Thomas Mossmann, Zoé J. Szczepek, Michal Wetzel, Max Machado, Rui Raden, Martin Miladi, Milad Kleinau, Gunnar Krüger, Christina Dembny, Paul Adler, Drew Zhai, Yuanyuan Kumbol, Victor Dzaye, Omar Schüler, Jutta Futschik, Matthias Backofen, Rolf Scheerer, Patrick Lehnardt, Seija |
dc.subject.por.fl_str_mv |
Extracellular microRNAs Endogenous Toll-like receptor ligands Cortical neurons Neuronal apoptosis Microglia Neurodegeneration miRNA microarray |
topic |
Extracellular microRNAs Endogenous Toll-like receptor ligands Cortical neurons Neuronal apoptosis Microglia Neurodegeneration miRNA microarray |
description |
Background: MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs’ sequence and structure required for this mode of action remained largely unresolved. Methods: Using a microarray-based screening approach we analyzed apoptotic cortical neurons of C56BL/6 mice and their supernatant with respect to alterations in miRNA expression/presence. HEK-Blue Toll-like receptor (TLR) 7/8 reporter cells, primary microglia and macrophages derived from human and mouse were employed to test the potential of the identified miRNAs released from apoptotic neurons to serve as signaling molecules for the RNAsensing receptors. Biophysical and bioinformatical approaches, as well as immunoassays and sequential microscopy were used to analyze the interaction between candidate miRNA and TLR. Immunocytochemical and -histochemical analyses of murine CNS cultures and adult mice intrathecally injected with miRNAs, respectively, were performed to evaluate the impact of miRNA-induced TLR activation on neuronal survival and microglial activation. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-12-15T10:47:54Z 2021-11-27 2021-11-27T00:00:00Z |
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/10400.1/17388 |
url |
http://hdl.handle.net/10400.1/17388 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1186/s13024-021-00498-5 1750-1326 |
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.publisher.none.fl_str_mv |
BMC |
publisher.none.fl_str_mv |
BMC |
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 |
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RCAAP |
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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) |
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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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