Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo

Autores
Dominguez Meijide, Antonio; Parrales, Valeria; Vasili, Eftychia; González Lizarraga, Maria Florencia; König, Annekatrin; Lázaro, Diana F.; Lannuzel, Annie; Haik, Stéphane; del Bel Belluz Guimaraes, Elaine; Chehin, Rosana Nieves; Raisman Vozari, Rita; Michel, Patrick P.; Bizat, Nicolas; Outeiro, Tiago Fleming
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.
Fil: Dominguez Meijide, Antonio. Universidad de Santiago de Compostela; España
Fil: Parrales, Valeria. Sorbonne University; Francia
Fil: Vasili, Eftychia. University Medical Center Goettingen; Alemania
Fil: González Lizarraga, Maria Florencia. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; Argentina
Fil: König, Annekatrin. University Medical Center Goettingen; Alemania
Fil: Lázaro, Diana F.. University Medical Center Goettingen; Alemania
Fil: Lannuzel, Annie. Sorbonne University; Francia
Fil: Haik, Stéphane. Sorbonne University; Francia
Fil: del Bel Belluz Guimaraes, Elaine. Universidade de Sao Paulo; Brasil
Fil: Chehin, Rosana Nieves. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; Argentina
Fil: Raisman Vozari, Rita. Sorbonne University; Francia
Fil: Michel, Patrick P.. Sorbonne University; Francia
Fil: Bizat, Nicolas. Sorbonne University; Francia
Fil: Outeiro, Tiago Fleming. University Medical Center Goettingen; Alemania
Materia
AGGREGATION
ALPHA-SYNUCLEIN
C. ELEGANS
DOXYCYCLINE
PARKINSON'S DISEASE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/172383
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/172383
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivoDominguez Meijide, AntonioParrales, ValeriaVasili, EftychiaGonzález Lizarraga, Maria FlorenciaKönig, AnnekatrinLázaro, Diana F.Lannuzel, AnnieHaik, Stéphanedel Bel Belluz Guimaraes, ElaineChehin, Rosana NievesRaisman Vozari, RitaMichel, Patrick P.Bizat, NicolasOuteiro, Tiago FlemingAGGREGATIONALPHA-SYNUCLEINC. ELEGANSDOXYCYCLINEPARKINSON'S DISEASEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.Fil: Dominguez Meijide, Antonio. Universidad de Santiago de Compostela; EspañaFil: Parrales, Valeria. Sorbonne University; FranciaFil: Vasili, Eftychia. University Medical Center Goettingen; AlemaniaFil: González Lizarraga, Maria Florencia. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; ArgentinaFil: König, Annekatrin. University Medical Center Goettingen; AlemaniaFil: Lázaro, Diana F.. University Medical Center Goettingen; AlemaniaFil: Lannuzel, Annie. Sorbonne University; FranciaFil: Haik, Stéphane. Sorbonne University; FranciaFil: del Bel Belluz Guimaraes, Elaine. Universidade de Sao Paulo; BrasilFil: Chehin, Rosana Nieves. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; ArgentinaFil: Raisman Vozari, Rita. Sorbonne University; FranciaFil: Michel, Patrick P.. Sorbonne University; FranciaFil: Bizat, Nicolas. Sorbonne University; FranciaFil: Outeiro, Tiago Fleming. University Medical Center Goettingen; AlemaniaAcademic Press Inc Elsevier Science2021-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/172383Dominguez Meijide, Antonio; Parrales, Valeria; Vasili, Eftychia; González Lizarraga, Maria Florencia; König, Annekatrin; et al.; Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo; Academic Press Inc Elsevier Science; Neurobiology of Disease; 151; 4-2021; 1-190969-99611095-953XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2021.105256info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S096999612100005Xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:32Zoai:ri.conicet.gov.ar:11336/172383instacron: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 09:59:32.53CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
title Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
spellingShingle Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
Dominguez Meijide, Antonio
AGGREGATION
ALPHA-SYNUCLEIN
C. ELEGANS
DOXYCYCLINE
PARKINSON'S DISEASE
title_short Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
title_full Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
title_fullStr Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
title_full_unstemmed Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
title_sort Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
dc.creator.none.fl_str_mv Dominguez Meijide, Antonio
Parrales, Valeria
Vasili, Eftychia
González Lizarraga, Maria Florencia
König, Annekatrin
Lázaro, Diana F.
Lannuzel, Annie
Haik, Stéphane
del Bel Belluz Guimaraes, Elaine
Chehin, Rosana Nieves
Raisman Vozari, Rita
Michel, Patrick P.
Bizat, Nicolas
Outeiro, Tiago Fleming
author Dominguez Meijide, Antonio
author_facet Dominguez Meijide, Antonio
Parrales, Valeria
Vasili, Eftychia
González Lizarraga, Maria Florencia
König, Annekatrin
Lázaro, Diana F.
Lannuzel, Annie
Haik, Stéphane
del Bel Belluz Guimaraes, Elaine
Chehin, Rosana Nieves
Raisman Vozari, Rita
Michel, Patrick P.
Bizat, Nicolas
Outeiro, Tiago Fleming
author_role author
author2 Parrales, Valeria
Vasili, Eftychia
González Lizarraga, Maria Florencia
König, Annekatrin
Lázaro, Diana F.
Lannuzel, Annie
Haik, Stéphane
del Bel Belluz Guimaraes, Elaine
Chehin, Rosana Nieves
Raisman Vozari, Rita
Michel, Patrick P.
Bizat, Nicolas
Outeiro, Tiago Fleming
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AGGREGATION
ALPHA-SYNUCLEIN
C. ELEGANS
DOXYCYCLINE
PARKINSON'S DISEASE
topic AGGREGATION
ALPHA-SYNUCLEIN
C. ELEGANS
DOXYCYCLINE
PARKINSON'S DISEASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.
Fil: Dominguez Meijide, Antonio. Universidad de Santiago de Compostela; España
Fil: Parrales, Valeria. Sorbonne University; Francia
Fil: Vasili, Eftychia. University Medical Center Goettingen; Alemania
Fil: González Lizarraga, Maria Florencia. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; Argentina
Fil: König, Annekatrin. University Medical Center Goettingen; Alemania
Fil: Lázaro, Diana F.. University Medical Center Goettingen; Alemania
Fil: Lannuzel, Annie. Sorbonne University; Francia
Fil: Haik, Stéphane. Sorbonne University; Francia
Fil: del Bel Belluz Guimaraes, Elaine. Universidade de Sao Paulo; Brasil
Fil: Chehin, Rosana Nieves. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; Argentina
Fil: Raisman Vozari, Rita. Sorbonne University; Francia
Fil: Michel, Patrick P.. Sorbonne University; Francia
Fil: Bizat, Nicolas. Sorbonne University; Francia
Fil: Outeiro, Tiago Fleming. University Medical Center Goettingen; Alemania
description Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.
publishDate 2021
dc.date.none.fl_str_mv 2021-04
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/11336/172383
Dominguez Meijide, Antonio; Parrales, Valeria; Vasili, Eftychia; González Lizarraga, Maria Florencia; König, Annekatrin; et al.; Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo; Academic Press Inc Elsevier Science; Neurobiology of Disease; 151; 4-2021; 1-19
0969-9961
1095-953X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/172383
identifier_str_mv Dominguez Meijide, Antonio; Parrales, Valeria; Vasili, Eftychia; González Lizarraga, Maria Florencia; König, Annekatrin; et al.; Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo; Academic Press Inc Elsevier Science; Neurobiology of Disease; 151; 4-2021; 1-19
0969-9961
1095-953X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2021.105256
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S096999612100005X
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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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