Allosteric modulation of α7 nicotinic receptors by flavonoids

Autores
Nielsen, Beatriz Elizabeth; Bermudez, Isabel; Bouzat, Cecilia Beatriz
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Plants have emerged as a valuable source for neuroprotective compounds like flavonoids. These polyphenolic com pounds decrease neurotoxicity and the development of neurodegeneration. Potentiation of α7 nicotinic receptor, which is involved in cognition and memory, is a potential therapeu tic strategy in neurodegenerative disorders. In particular, positive allosteric modulators (PAMs) are emerging as the best therapeutic tools. Some flavonoids have been reported as ligands for α7 , but the molecular mechanisms underlying this interaction remain unknown. Our main goal is to unrav el the molecular basis of flavonoid action at α7 by electro physiological techniques. We analyzed the effects of prototypes of distinct classes of flavonoids: quercetin, genistein, and 7-dihydroxy-4-phenylcoumarin (neoflavonoid) on α7 activity. At the macroscopic level, the three compounds increased the peak current elicited by acetylcholine with minimal effects on desensitization, indicating that they behave as type I PAMs. At the single-channel level, they increased, with different efficacies, the duration of the open state. By analyzing the effects of flavonoids on mutant and chimeric α7 receptors, we found that they share the transmembrane structural determinants of poten tiation known for other PAMs. We conclude that, in addition to the well-known effects as antioxidants, the unique properties of flavonoids as natural α7 PAMs make them candidate compounds for the treatment of neurodegenerative disorders.
Fil: Nielsen, Beatriz Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bermudez, Isabel. University of Oxford; Reino Unido
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
XXXIII Congress of the Argentine Society for Research in Neuroscience
Córdoba
Argentina
American Society for Neurochemistry
Materia
FLAVONOIDS
ALPHA7 NICOTINIC RECEPTOR
ALLOSTERIC MODULATORS
PATCH CLAMP
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/156671
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Allosteric modulation of α7 nicotinic receptors by flavonoidsNielsen, Beatriz ElizabethBermudez, IsabelBouzat, Cecilia BeatrizFLAVONOIDSALPHA7 NICOTINIC RECEPTORALLOSTERIC MODULATORSPATCH CLAMPhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Plants have emerged as a valuable source for neuroprotective compounds like flavonoids. These polyphenolic com pounds decrease neurotoxicity and the development of neurodegeneration. Potentiation of α7 nicotinic receptor, which is involved in cognition and memory, is a potential therapeu tic strategy in neurodegenerative disorders. In particular, positive allosteric modulators (PAMs) are emerging as the best therapeutic tools. Some flavonoids have been reported as ligands for α7 , but the molecular mechanisms underlying this interaction remain unknown. Our main goal is to unrav el the molecular basis of flavonoid action at α7 by electro physiological techniques. We analyzed the effects of prototypes of distinct classes of flavonoids: quercetin, genistein, and 7-dihydroxy-4-phenylcoumarin (neoflavonoid) on α7 activity. At the macroscopic level, the three compounds increased the peak current elicited by acetylcholine with minimal effects on desensitization, indicating that they behave as type I PAMs. At the single-channel level, they increased, with different efficacies, the duration of the open state. By analyzing the effects of flavonoids on mutant and chimeric α7 receptors, we found that they share the transmembrane structural determinants of poten tiation known for other PAMs. We conclude that, in addition to the well-known effects as antioxidants, the unique properties of flavonoids as natural α7 PAMs make them candidate compounds for the treatment of neurodegenerative disorders.Fil: Nielsen, Beatriz Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Bermudez, Isabel. University of Oxford; Reino UnidoFil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaXXXIII Congress of the Argentine Society for Research in NeuroscienceCórdobaArgentinaAmerican Society for NeurochemistrySAGE Publications2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/156671Allosteric modulation of α7 nicotinic receptors by flavonoids; XXXIII Congress of the Argentine Society for Research in Neuroscience; Córdoba; Argentina; 2018; 120-1201759-0914CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/info:eu-repo/semantics/altIdentifier/doi/10.1177/1759091419834821Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:23Zoai:ri.conicet.gov.ar:11336/156671instacron: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:34982025-09-29 09:32:23.536CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Allosteric modulation of α7 nicotinic receptors by flavonoids
title Allosteric modulation of α7 nicotinic receptors by flavonoids
spellingShingle Allosteric modulation of α7 nicotinic receptors by flavonoids
Nielsen, Beatriz Elizabeth
FLAVONOIDS
ALPHA7 NICOTINIC RECEPTOR
ALLOSTERIC MODULATORS
PATCH CLAMP
title_short Allosteric modulation of α7 nicotinic receptors by flavonoids
title_full Allosteric modulation of α7 nicotinic receptors by flavonoids
title_fullStr Allosteric modulation of α7 nicotinic receptors by flavonoids
title_full_unstemmed Allosteric modulation of α7 nicotinic receptors by flavonoids
title_sort Allosteric modulation of α7 nicotinic receptors by flavonoids
dc.creator.none.fl_str_mv Nielsen, Beatriz Elizabeth
Bermudez, Isabel
Bouzat, Cecilia Beatriz
author Nielsen, Beatriz Elizabeth
author_facet Nielsen, Beatriz Elizabeth
Bermudez, Isabel
Bouzat, Cecilia Beatriz
author_role author
author2 Bermudez, Isabel
Bouzat, Cecilia Beatriz
author2_role author
author
dc.subject.none.fl_str_mv FLAVONOIDS
ALPHA7 NICOTINIC RECEPTOR
ALLOSTERIC MODULATORS
PATCH CLAMP
topic FLAVONOIDS
ALPHA7 NICOTINIC RECEPTOR
ALLOSTERIC MODULATORS
PATCH CLAMP
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Plants have emerged as a valuable source for neuroprotective compounds like flavonoids. These polyphenolic com pounds decrease neurotoxicity and the development of neurodegeneration. Potentiation of α7 nicotinic receptor, which is involved in cognition and memory, is a potential therapeu tic strategy in neurodegenerative disorders. In particular, positive allosteric modulators (PAMs) are emerging as the best therapeutic tools. Some flavonoids have been reported as ligands for α7 , but the molecular mechanisms underlying this interaction remain unknown. Our main goal is to unrav el the molecular basis of flavonoid action at α7 by electro physiological techniques. We analyzed the effects of prototypes of distinct classes of flavonoids: quercetin, genistein, and 7-dihydroxy-4-phenylcoumarin (neoflavonoid) on α7 activity. At the macroscopic level, the three compounds increased the peak current elicited by acetylcholine with minimal effects on desensitization, indicating that they behave as type I PAMs. At the single-channel level, they increased, with different efficacies, the duration of the open state. By analyzing the effects of flavonoids on mutant and chimeric α7 receptors, we found that they share the transmembrane structural determinants of poten tiation known for other PAMs. We conclude that, in addition to the well-known effects as antioxidants, the unique properties of flavonoids as natural α7 PAMs make them candidate compounds for the treatment of neurodegenerative disorders.
Fil: Nielsen, Beatriz Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Bermudez, Isabel. University of Oxford; Reino Unido
Fil: Bouzat, Cecilia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
XXXIII Congress of the Argentine Society for Research in Neuroscience
Córdoba
Argentina
American Society for Neurochemistry
description Plants have emerged as a valuable source for neuroprotective compounds like flavonoids. These polyphenolic com pounds decrease neurotoxicity and the development of neurodegeneration. Potentiation of α7 nicotinic receptor, which is involved in cognition and memory, is a potential therapeu tic strategy in neurodegenerative disorders. In particular, positive allosteric modulators (PAMs) are emerging as the best therapeutic tools. Some flavonoids have been reported as ligands for α7 , but the molecular mechanisms underlying this interaction remain unknown. Our main goal is to unrav el the molecular basis of flavonoid action at α7 by electro physiological techniques. We analyzed the effects of prototypes of distinct classes of flavonoids: quercetin, genistein, and 7-dihydroxy-4-phenylcoumarin (neoflavonoid) on α7 activity. At the macroscopic level, the three compounds increased the peak current elicited by acetylcholine with minimal effects on desensitization, indicating that they behave as type I PAMs. At the single-channel level, they increased, with different efficacies, the duration of the open state. By analyzing the effects of flavonoids on mutant and chimeric α7 receptors, we found that they share the transmembrane structural determinants of poten tiation known for other PAMs. We conclude that, in addition to the well-known effects as antioxidants, the unique properties of flavonoids as natural α7 PAMs make them candidate compounds for the treatment of neurodegenerative disorders.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/156671
Allosteric modulation of α7 nicotinic receptors by flavonoids; XXXIII Congress of the Argentine Society for Research in Neuroscience; Córdoba; Argentina; 2018; 120-120
1759-0914
CONICET Digital
CONICET
url http://hdl.handle.net/11336/156671
identifier_str_mv Allosteric modulation of α7 nicotinic receptors by flavonoids; XXXIII Congress of the Argentine Society for Research in Neuroscience; Córdoba; Argentina; 2018; 120-120
1759-0914
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://saneurociencias.org.ar/
info:eu-repo/semantics/altIdentifier/doi/10.1177/1759091419834821
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv SAGE Publications
publisher.none.fl_str_mv SAGE Publications
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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 13.069144

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