Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors
- Autores
- Bouzat, Cecilia Beatriz
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- The α7 nicotinic acetylcholine receptor is a pentameric ligand gated ion channel. It is widely expressed in the central nervous system where it is involved in cognition, attention, and memory. It is also expressed in many non-neuronal cells and its activation has anti-inflammatory and neuroprotective roles. Enhancement of α7 activity is emerging as a therapeutic strategy for cognitive, neurodegenerative and inflammatory disorders. We have focused on understanding α7 function and its different mechanisms of modulation associated to physiological, pathological and therapeutic situations. By single-channel recordings we determined that positive allosteric modulators (PAMs) enhance α7 activation by increasing open-channel lifetime and inducing prolonged activation episodes, and we also identified novel PAMs. Although α7 has been considered the homomeric member of the family, heteromeric α7β2 receptors have been detected in human brain. We generated α7β2 receptors with different stoichiometries and determined how the β2 subunit modifies α7 kinetics and its allosteric modulation. This information is required to decipher the role of α7β2 receptors in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from partial duplication of the α7 gene. We demonstrated that dupα7 acts as a negative modulator and can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 function has implications for the design of novel therapeutic compounds as well as for clarifying its pleiotropic actions.
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XLI Congreso Anual de la Sociedad de Farmacología de Chile
Concepción
Chile
Sociedad de Farmacología de Chile
Universidad de Concepción - Materia
-
NICOTINIC RECEPTORS
ION CHANNELS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/174519
Ver los metadatos del registro completo
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Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptorsBouzat, Cecilia BeatrizNICOTINIC RECEPTORSION CHANNELShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The α7 nicotinic acetylcholine receptor is a pentameric ligand gated ion channel. It is widely expressed in the central nervous system where it is involved in cognition, attention, and memory. It is also expressed in many non-neuronal cells and its activation has anti-inflammatory and neuroprotective roles. Enhancement of α7 activity is emerging as a therapeutic strategy for cognitive, neurodegenerative and inflammatory disorders. We have focused on understanding α7 function and its different mechanisms of modulation associated to physiological, pathological and therapeutic situations. By single-channel recordings we determined that positive allosteric modulators (PAMs) enhance α7 activation by increasing open-channel lifetime and inducing prolonged activation episodes, and we also identified novel PAMs. Although α7 has been considered the homomeric member of the family, heteromeric α7β2 receptors have been detected in human brain. We generated α7β2 receptors with different stoichiometries and determined how the β2 subunit modifies α7 kinetics and its allosteric modulation. This information is required to decipher the role of α7β2 receptors in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from partial duplication of the α7 gene. We demonstrated that dupα7 acts as a negative modulator and can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 function has implications for the design of novel therapeutic compounds as well as for clarifying its pleiotropic actions.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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaXLI Congreso Anual de la Sociedad de Farmacología de ChileConcepciónChileSociedad de Farmacología de ChileUniversidad de ConcepciónSociedad de Farmacología de Chile2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/174519Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors; XLI Congreso Anual de la Sociedad de Farmacología de Chile; Concepción; Chile; 2019; 4-50718-8811CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sofarchi.cl/info:eu-repo/semantics/altIdentifier/url/https://www.sofarchi.cl/wp-content/uploads/Revista-SOFARCHI-Final-Res%C3%BAmenes-Vol-12-N3-2019.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:00:34Zoai:ri.conicet.gov.ar:11336/174519instacron: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 10:00:34.549CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors |
| title |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors |
| spellingShingle |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors Bouzat, Cecilia Beatriz NICOTINIC RECEPTORS ION CHANNELS |
| title_short |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors |
| title_full |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors |
| title_fullStr |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors |
| title_full_unstemmed |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors |
| title_sort |
Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors |
| dc.creator.none.fl_str_mv |
Bouzat, Cecilia Beatriz |
| author |
Bouzat, Cecilia Beatriz |
| author_facet |
Bouzat, Cecilia Beatriz |
| author_role |
author |
| dc.subject.none.fl_str_mv |
NICOTINIC RECEPTORS ION CHANNELS |
| topic |
NICOTINIC RECEPTORS ION CHANNELS |
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https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
The α7 nicotinic acetylcholine receptor is a pentameric ligand gated ion channel. It is widely expressed in the central nervous system where it is involved in cognition, attention, and memory. It is also expressed in many non-neuronal cells and its activation has anti-inflammatory and neuroprotective roles. Enhancement of α7 activity is emerging as a therapeutic strategy for cognitive, neurodegenerative and inflammatory disorders. We have focused on understanding α7 function and its different mechanisms of modulation associated to physiological, pathological and therapeutic situations. By single-channel recordings we determined that positive allosteric modulators (PAMs) enhance α7 activation by increasing open-channel lifetime and inducing prolonged activation episodes, and we also identified novel PAMs. Although α7 has been considered the homomeric member of the family, heteromeric α7β2 receptors have been detected in human brain. We generated α7β2 receptors with different stoichiometries and determined how the β2 subunit modifies α7 kinetics and its allosteric modulation. This information is required to decipher the role of α7β2 receptors in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from partial duplication of the α7 gene. We demonstrated that dupα7 acts as a negative modulator and can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 function has implications for the design of novel therapeutic compounds as well as for clarifying its pleiotropic actions. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina XLI Congreso Anual de la Sociedad de Farmacología de Chile Concepción Chile Sociedad de Farmacología de Chile Universidad de Concepción |
| description |
The α7 nicotinic acetylcholine receptor is a pentameric ligand gated ion channel. It is widely expressed in the central nervous system where it is involved in cognition, attention, and memory. It is also expressed in many non-neuronal cells and its activation has anti-inflammatory and neuroprotective roles. Enhancement of α7 activity is emerging as a therapeutic strategy for cognitive, neurodegenerative and inflammatory disorders. We have focused on understanding α7 function and its different mechanisms of modulation associated to physiological, pathological and therapeutic situations. By single-channel recordings we determined that positive allosteric modulators (PAMs) enhance α7 activation by increasing open-channel lifetime and inducing prolonged activation episodes, and we also identified novel PAMs. Although α7 has been considered the homomeric member of the family, heteromeric α7β2 receptors have been detected in human brain. We generated α7β2 receptors with different stoichiometries and determined how the β2 subunit modifies α7 kinetics and its allosteric modulation. This information is required to decipher the role of α7β2 receptors in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from partial duplication of the α7 gene. We demonstrated that dupα7 acts as a negative modulator and can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 function has implications for the design of novel therapeutic compounds as well as for clarifying its pleiotropic actions. |
| publishDate |
2019 |
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2019 |
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http://hdl.handle.net/11336/174519 Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors; XLI Congreso Anual de la Sociedad de Farmacología de Chile; Concepción; Chile; 2019; 4-5 0718-8811 CONICET Digital CONICET |
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Genetic, protein and pharmacological modulation of human alpha7 nicotinic receptors; XLI Congreso Anual de la Sociedad de Farmacología de Chile; Concepción; Chile; 2019; 4-5 0718-8811 CONICET Digital CONICET |
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eng |
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eng |
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