Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates

Autores
Acuña, Leonardo; Hamadat, Sabah; Corbalan, Natalia Soledad; González Lizarraga, Maria Florencia; Dos Santos Pereira, Mauricio; Rocca, Jérémy; Sepúlveda Díaz, Julia; Del Bel, Elaine; Papy García, Dulce; Chehin, Rosana Nieves; Michel, Patrick P.; Raisman Vozari, Rita
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Abstract: Aggregated forms of the synaptic protein α‐synuclein (αS) have been proposed to operateas a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´sdisease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinanthuman αS to assess the anti‐inflammatory and neuroprotective activities of the antibiotic rifampicin(Rif) and its autoxidation product rifampicin quinone (RifQ). Pretreatments with Rif and RifQreduced the secretion of prototypical inflammatory cytokines (TNF‐, IL‐6) and the burst ofoxidative stress in microglial cells activated with αS fibrillary aggregates. Note, however, that RifQwas constantly more efficacious than its parent compound in reducing microglial activation. Wealso established that the suppressive effects of Rif and RifQ on cytokine release was probably dueto inhibition of both PI3K‐ and non‐PI3K‐dependent signaling events. The control of oxidative stressappeared, however, essentially dependent on PI3K inhibition. Of interest, we also showed that RifQwas more efficient than Rif in protecting neuronal cells from toxic factors secreted by microgliaactivated by αS fibrils. Overall, data with RifQ are promising enough to justify further studies toconfirm the potential of this compound as an anti‐parkinsionian drug.
Fil: Acuña, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Hamadat, Sabah. Sorbonne University; Francia
Fil: Corbalan, Natalia Soledad. Université Paris Est Créteil; Francia. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; Argentina
Fil: González Lizarraga, Maria Florencia. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; Argentina
Fil: Dos Santos Pereira, Mauricio. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia. Universidade de Sao Paulo; Brasil
Fil: Rocca, Jérémy. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Sepúlveda Díaz, Julia. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Del Bel, Elaine. Universidade de Sao Paulo; Brasil
Fil: Papy García, Dulce. Université Paris Est Créteil; Francia
Fil: Chehin, Rosana Nieves. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; Argentina
Fil: Michel, Patrick P.. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Raisman Vozari, Rita. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Materia
AGGREGATION
MICROGLIA
NEUROINFLAMMATION
PARKINSON'S DISEASE
CYTOKINES
NEURONAL SURVIVAL
A-SYNUCLEIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/120492
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary AggregatesAcuña, LeonardoHamadat, SabahCorbalan, Natalia SoledadGonzález Lizarraga, Maria FlorenciaDos Santos Pereira, MauricioRocca, JérémySepúlveda Díaz, JuliaDel Bel, ElainePapy García, DulceChehin, Rosana NievesMichel, Patrick P.Raisman Vozari, RitaAGGREGATIONMICROGLIANEUROINFLAMMATIONPARKINSON'S DISEASECYTOKINESNEURONAL SURVIVALA-SYNUCLEINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Abstract: Aggregated forms of the synaptic protein α‐synuclein (αS) have been proposed to operateas a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´sdisease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinanthuman αS to assess the anti‐inflammatory and neuroprotective activities of the antibiotic rifampicin(Rif) and its autoxidation product rifampicin quinone (RifQ). Pretreatments with Rif and RifQreduced the secretion of prototypical inflammatory cytokines (TNF‐, IL‐6) and the burst ofoxidative stress in microglial cells activated with αS fibrillary aggregates. Note, however, that RifQwas constantly more efficacious than its parent compound in reducing microglial activation. Wealso established that the suppressive effects of Rif and RifQ on cytokine release was probably dueto inhibition of both PI3K‐ and non‐PI3K‐dependent signaling events. The control of oxidative stressappeared, however, essentially dependent on PI3K inhibition. Of interest, we also showed that RifQwas more efficient than Rif in protecting neuronal cells from toxic factors secreted by microgliaactivated by αS fibrils. Overall, data with RifQ are promising enough to justify further studies toconfirm the potential of this compound as an anti‐parkinsionian drug.Fil: Acuña, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Sorbonne University; Francia. Centre National de la Recherche Scientifique; FranciaFil: Hamadat, Sabah. Sorbonne University; FranciaFil: Corbalan, Natalia Soledad. Université Paris Est Créteil; Francia. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: González Lizarraga, Maria Florencia. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Dos Santos Pereira, Mauricio. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia. Universidade de Sao Paulo; BrasilFil: Rocca, Jérémy. Sorbonne University; Francia. Centre National de la Recherche Scientifique; FranciaFil: Sepúlveda Díaz, Julia. Sorbonne University; Francia. Centre National de la Recherche Scientifique; FranciaFil: Del Bel, Elaine. Universidade de Sao Paulo; BrasilFil: Papy García, Dulce. Université Paris Est Créteil; FranciaFil: Chehin, Rosana Nieves. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; ArgentinaFil: Michel, Patrick P.. Sorbonne University; Francia. Centre National de la Recherche Scientifique; FranciaFil: Raisman Vozari, Rita. Sorbonne University; Francia. Centre National de la Recherche Scientifique; FranciaMultidisciplinary Digital Publishing Institute2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/120492Acuña, Leonardo; Hamadat, Sabah; Corbalan, Natalia Soledad; González Lizarraga, Maria Florencia; Dos Santos Pereira, Mauricio; et al.; Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates; Multidisciplinary Digital Publishing Institute; Cells; 8; 8; 2019; 1-172073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/8/8/776info:eu-repo/semantics/altIdentifier/doi/10.3390/cells8080776info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:49Zoai:ri.conicet.gov.ar:11336/120492instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:49.812CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
title Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
spellingShingle Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
Acuña, Leonardo
AGGREGATION
MICROGLIA
NEUROINFLAMMATION
PARKINSON'S DISEASE
CYTOKINES
NEURONAL SURVIVAL
A-SYNUCLEIN
title_short Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
title_full Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
title_fullStr Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
title_full_unstemmed Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
title_sort Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates
dc.creator.none.fl_str_mv Acuña, Leonardo
Hamadat, Sabah
Corbalan, Natalia Soledad
González Lizarraga, Maria Florencia
Dos Santos Pereira, Mauricio
Rocca, Jérémy
Sepúlveda Díaz, Julia
Del Bel, Elaine
Papy García, Dulce
Chehin, Rosana Nieves
Michel, Patrick P.
Raisman Vozari, Rita
author Acuña, Leonardo
author_facet Acuña, Leonardo
Hamadat, Sabah
Corbalan, Natalia Soledad
González Lizarraga, Maria Florencia
Dos Santos Pereira, Mauricio
Rocca, Jérémy
Sepúlveda Díaz, Julia
Del Bel, Elaine
Papy García, Dulce
Chehin, Rosana Nieves
Michel, Patrick P.
Raisman Vozari, Rita
author_role author
author2 Hamadat, Sabah
Corbalan, Natalia Soledad
González Lizarraga, Maria Florencia
Dos Santos Pereira, Mauricio
Rocca, Jérémy
Sepúlveda Díaz, Julia
Del Bel, Elaine
Papy García, Dulce
Chehin, Rosana Nieves
Michel, Patrick P.
Raisman Vozari, Rita
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AGGREGATION
MICROGLIA
NEUROINFLAMMATION
PARKINSON'S DISEASE
CYTOKINES
NEURONAL SURVIVAL
A-SYNUCLEIN
topic AGGREGATION
MICROGLIA
NEUROINFLAMMATION
PARKINSON'S DISEASE
CYTOKINES
NEURONAL SURVIVAL
A-SYNUCLEIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Abstract: Aggregated forms of the synaptic protein α‐synuclein (αS) have been proposed to operateas a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´sdisease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinanthuman αS to assess the anti‐inflammatory and neuroprotective activities of the antibiotic rifampicin(Rif) and its autoxidation product rifampicin quinone (RifQ). Pretreatments with Rif and RifQreduced the secretion of prototypical inflammatory cytokines (TNF‐, IL‐6) and the burst ofoxidative stress in microglial cells activated with αS fibrillary aggregates. Note, however, that RifQwas constantly more efficacious than its parent compound in reducing microglial activation. Wealso established that the suppressive effects of Rif and RifQ on cytokine release was probably dueto inhibition of both PI3K‐ and non‐PI3K‐dependent signaling events. The control of oxidative stressappeared, however, essentially dependent on PI3K inhibition. Of interest, we also showed that RifQwas more efficient than Rif in protecting neuronal cells from toxic factors secreted by microgliaactivated by αS fibrils. Overall, data with RifQ are promising enough to justify further studies toconfirm the potential of this compound as an anti‐parkinsionian drug.
Fil: Acuña, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Hamadat, Sabah. Sorbonne University; Francia
Fil: Corbalan, Natalia Soledad. Université Paris Est Créteil; Francia. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; Argentina
Fil: González Lizarraga, Maria Florencia. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; Argentina
Fil: Dos Santos Pereira, Mauricio. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia. Universidade de Sao Paulo; Brasil
Fil: Rocca, Jérémy. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Sepúlveda Díaz, Julia. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Del Bel, Elaine. Universidade de Sao Paulo; Brasil
Fil: Papy García, Dulce. Université Paris Est Créteil; Francia
Fil: Chehin, Rosana Nieves. Universidad Nacional de Tucuman. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucuman. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet Noa Sur. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario.; Argentina
Fil: Michel, Patrick P.. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Raisman Vozari, Rita. Sorbonne University; Francia. Centre National de la Recherche Scientifique; Francia
description Abstract: Aggregated forms of the synaptic protein α‐synuclein (αS) have been proposed to operateas a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´sdisease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinanthuman αS to assess the anti‐inflammatory and neuroprotective activities of the antibiotic rifampicin(Rif) and its autoxidation product rifampicin quinone (RifQ). Pretreatments with Rif and RifQreduced the secretion of prototypical inflammatory cytokines (TNF‐, IL‐6) and the burst ofoxidative stress in microglial cells activated with αS fibrillary aggregates. Note, however, that RifQwas constantly more efficacious than its parent compound in reducing microglial activation. Wealso established that the suppressive effects of Rif and RifQ on cytokine release was probably dueto inhibition of both PI3K‐ and non‐PI3K‐dependent signaling events. The control of oxidative stressappeared, however, essentially dependent on PI3K inhibition. Of interest, we also showed that RifQwas more efficient than Rif in protecting neuronal cells from toxic factors secreted by microgliaactivated by αS fibrils. Overall, data with RifQ are promising enough to justify further studies toconfirm the potential of this compound as an anti‐parkinsionian drug.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/120492
Acuña, Leonardo; Hamadat, Sabah; Corbalan, Natalia Soledad; González Lizarraga, Maria Florencia; Dos Santos Pereira, Mauricio; et al.; Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates; Multidisciplinary Digital Publishing Institute; Cells; 8; 8; 2019; 1-17
2073-4409
CONICET Digital
CONICET
url http://hdl.handle.net/11336/120492
identifier_str_mv Acuña, Leonardo; Hamadat, Sabah; Corbalan, Natalia Soledad; González Lizarraga, Maria Florencia; Dos Santos Pereira, Mauricio; et al.; Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates; Multidisciplinary Digital Publishing Institute; Cells; 8; 8; 2019; 1-17
2073-4409
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/8/8/776
info:eu-repo/semantics/altIdentifier/doi/10.3390/cells8080776
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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