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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/156671
Ver los metadatos del registro completo
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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 Técnicas2025-09-03T09:43:18Zoai: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:34982025-09-03 09:43:18.664CONICET 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 |
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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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.13397 |