The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease

Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this...

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Autores: Alonso, Eva, Vale González, María del Carmen, Rodríguez Vieytes, Mercedes, Laferla, Frank M., Giménez-Llort, Lydia, Botana López, Luis Miguel
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:dnet:minerva_____::1d6a5f0d27d31e626e72e262321a68c1
Acceso en línea:https://hdl.handle.net/10347/47339
Access Level:acceso abierto
Palabra clave:Gymnodimine
Alzheimer disease
Tau protein
Beta-amyloid
Acetylcholine
Investigación
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spelling The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer diseaseAlonso, EvaVale González, María del CarmenRodríguez Vieytes, MercedesLaferla, Frank M.Giménez-Llort, LydiaBotana López, Luis MiguelGymnodimineAlzheimer diseaseTau proteinBeta-amyloidAcetylcholineInvestigaciónGymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology in vitro. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity in vitro. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases.KargerUniversidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía FarmacéuticaUniversidade de Santiago de Compostela. Departamento de Fisioloxía20112011-06-1720112011-06-17journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10347/47339reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)InglésengMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental SAF2009-12581 Evaluacion In Vitro De Compuestos Bioactivos De Origen Marino Para Su Empleo En Enfermedades NeurodegenerativasMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental AGL2009-13581-C02-01 Evaluacion De Los Riesgos De Salud Publica Debidos A Toxinas Marinas De Aguas Templadas En Las Costas Europeas Y Del Efecto Sinergico Con Otras Toxinas Habituales En Estas Latitudes. Subproyecto 2Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental TRA2009-0189 Desarrollo de un prototipo en formato kit para la detección rápida de iminas cíclicas en microplacaMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental AGL2010-17875 IMPLICACIONES ALIMENTARIAS DE LA PRESENCIA DE NUEVAS TOXINAS EN EL MARISCO ESPAÑOLEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 211326-CPEuropean Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 265896European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 265409European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 262649open accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dnet:minerva_____::1d6a5f0d27d31e626e72e262321a68c12026-06-15T12:47:27Z
dc.title.none.fl_str_mv The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
title The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
spellingShingle The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
Alonso, Eva
Gymnodimine
Alzheimer disease
Tau protein
Beta-amyloid
Acetylcholine
Investigación
title_short The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
title_full The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
title_fullStr The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
title_full_unstemmed The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
title_sort The cholinergic antagonist gymnodimine improves Aβ and tau neuropathology in an in vitro model of Alzheimer disease
dc.creator.none.fl_str_mv Alonso, Eva
Vale González, María del Carmen
Rodríguez Vieytes, Mercedes
Laferla, Frank M.
Giménez-Llort, Lydia
Botana López, Luis Miguel
author Alonso, Eva
author_facet Alonso, Eva
Vale González, María del Carmen
Rodríguez Vieytes, Mercedes
Laferla, Frank M.
Giménez-Llort, Lydia
Botana López, Luis Miguel
author_role author
author2 Vale González, María del Carmen
Rodríguez Vieytes, Mercedes
Laferla, Frank M.
Giménez-Llort, Lydia
Botana López, Luis Miguel
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Universidade de Santiago de Compostela. Departamento de Fisioloxía
dc.subject.none.fl_str_mv Gymnodimine
Alzheimer disease
Tau protein
Beta-amyloid
Acetylcholine
Investigación
topic Gymnodimine
Alzheimer disease
Tau protein
Beta-amyloid
Acetylcholine
Investigación
description Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposure of cortical neurons to gymnodimine in the progress of Alzheimer disease (AD) pathology in vitro. Treatment of cortical neurons with 50 nM gymnodimine decreased the intracellular amyloid beta (Aβ) accumulation and the levels of the hyperphosphorylated isoforms of tau protein recognized by AT8 and AT100 antibodies. These results are suggested to be mediated by the increase in the inactive isoform of the glycogen synthase kinase-3 (phospho GSK-3 Ser9), the decrease in the levels of the active isoform of the ERK1/2 kinase and the increase in acetylcholine (Ach) synthesis elicited by long term exposure of cortical neurons to the toxin. Moreover, gymnodimine decreased glutamate-induced neurotoxicity in vitro. Altogether these results indicate that the marine phycotoxin gymnodimine may constitute a valuable tool for the development of drugs to treat neurodegenerative diseases.
publishDate 2011
dc.date.none.fl_str_mv 2011
2011-06-17
2011
2011-06-17
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10347/47339
url https://hdl.handle.net/10347/47339
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental SAF2009-12581 Evaluacion In Vitro De Compuestos Bioactivos De Origen Marino Para Su Empleo En Enfermedades Neurodegenerativas
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental AGL2009-13581-C02-01 Evaluacion De Los Riesgos De Salud Publica Debidos A Toxinas Marinas De Aguas Templadas En Las Costas Europeas Y Del Efecto Sinergico Con Otras Toxinas Habituales En Estas Latitudes. Subproyecto 2
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental TRA2009-0189 Desarrollo de un prototipo en formato kit para la detección rápida de iminas cíclicas en microplaca
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Programa Nacional de Investigación Fundamental AGL2010-17875 IMPLICACIONES ALIMENTARIAS DE LA PRESENCIA DE NUEVAS TOXINAS EN EL MARISCO ESPAÑOL
European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 211326-CP
European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 265896
European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 265409
European Commission http://dx.doi.org/10.13039/501100000780 Seventh Framework Programme 262649
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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