Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target
- Autores
- Bouzat, Cecilia Beatriz
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- The α7 nicotinic receptor is a pentameric ligand-gated ion channel widely expressed in the central nervous system, where it plays key roles in cognition, attention, and memory. It is also found in non-neuronal cells, contributing to anti- inflammatory and neuroprotective processes. The enhancement of α7 activity is emerging as a promising therapeutic strategy for neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, as well as neurological and inflammatory conditions. Despite promising preclinical and clinical data, no α7- specific ligand has been approved for clinical use yet. Our objective is to elucidate the molecular function of α7 and its modulation under physiological and pathological conditions, in order to advance its potential as a therapeutic target. We expressed α7 in mammalian cells and assessed its function using single- channel and macroscopic current patch-clamp recordings. Through this approach, we identified natural and synthetic compounds that act as novel α7 positive allosteric modulators, exhibiting neuroprotective properties and offering new molecules with therapeutic potential. Additionally, we characterized new mechanisms of α7 modulation, including interactions with oligomeric amyloid beta peptides associated with Alzheimer's disease, cannabidiol, phosphorylation, calcium, and other nicotinic receptor subunits. These findings provide critical insights to be considered in future clinical trials. By investigating α7 function from a molecular perspective, our results lay the groundwork for its implementation as a viable therapeutic drug target.
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
LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina de Farmacología Experimental - Materia
-
LIGAND-GATED ION CHANNEL
PATCH CLAMP
NICOTINIC RECEPTOR
ALPHA7 - 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:11336/251350
Ver los metadatos del registro completo
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Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug targetBouzat, Cecilia BeatrizLIGAND-GATED ION CHANNELPATCH CLAMPNICOTINIC RECEPTORALPHA7https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The α7 nicotinic receptor is a pentameric ligand-gated ion channel widely expressed in the central nervous system, where it plays key roles in cognition, attention, and memory. It is also found in non-neuronal cells, contributing to anti- inflammatory and neuroprotective processes. The enhancement of α7 activity is emerging as a promising therapeutic strategy for neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, as well as neurological and inflammatory conditions. Despite promising preclinical and clinical data, no α7- specific ligand has been approved for clinical use yet. Our objective is to elucidate the molecular function of α7 and its modulation under physiological and pathological conditions, in order to advance its potential as a therapeutic target. We expressed α7 in mammalian cells and assessed its function using single- channel and macroscopic current patch-clamp recordings. Through this approach, we identified natural and synthetic compounds that act as novel α7 positive allosteric modulators, exhibiting neuroprotective properties and offering new molecules with therapeutic potential. Additionally, we characterized new mechanisms of α7 modulation, including interactions with oligomeric amyloid beta peptides associated with Alzheimer's disease, cannabidiol, phosphorylation, calcium, and other nicotinic receptor subunits. These findings provide critical insights to be considered in future clinical trials. By investigating α7 function from a molecular perspective, our results lay the groundwork for its implementation as a viable therapeutic drug target.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; ArgentinaLVI Reunión Anual de la Asociación Argentina de Farmacología ExperimentalBahía BlancaArgentinaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Farmacología Experimental2024info: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/11336/251350Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target; LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental; Bahía Blanca; Argentina; 2024; 19-19CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:10:23Zoai:ri.conicet.gov.ar:11336/251350instacron: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:34982025-09-10 13:10:24.122CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target |
| title |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target |
| spellingShingle |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target Bouzat, Cecilia Beatriz LIGAND-GATED ION CHANNEL PATCH CLAMP NICOTINIC RECEPTOR ALPHA7 |
| title_short |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target |
| title_full |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target |
| title_fullStr |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target |
| title_full_unstemmed |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target |
| title_sort |
Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target |
| 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 |
LIGAND-GATED ION CHANNEL PATCH CLAMP NICOTINIC RECEPTOR ALPHA7 |
| topic |
LIGAND-GATED ION CHANNEL PATCH CLAMP NICOTINIC RECEPTOR ALPHA7 |
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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 receptor is a pentameric ligand-gated ion channel widely expressed in the central nervous system, where it plays key roles in cognition, attention, and memory. It is also found in non-neuronal cells, contributing to anti- inflammatory and neuroprotective processes. The enhancement of α7 activity is emerging as a promising therapeutic strategy for neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, as well as neurological and inflammatory conditions. Despite promising preclinical and clinical data, no α7- specific ligand has been approved for clinical use yet. Our objective is to elucidate the molecular function of α7 and its modulation under physiological and pathological conditions, in order to advance its potential as a therapeutic target. We expressed α7 in mammalian cells and assessed its function using single- channel and macroscopic current patch-clamp recordings. Through this approach, we identified natural and synthetic compounds that act as novel α7 positive allosteric modulators, exhibiting neuroprotective properties and offering new molecules with therapeutic potential. Additionally, we characterized new mechanisms of α7 modulation, including interactions with oligomeric amyloid beta peptides associated with Alzheimer's disease, cannabidiol, phosphorylation, calcium, and other nicotinic receptor subunits. These findings provide critical insights to be considered in future clinical trials. By investigating α7 function from a molecular perspective, our results lay the groundwork for its implementation as a viable therapeutic drug target. 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 LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental Bahía Blanca Argentina Asociación Argentina de Farmacología Experimental |
| description |
The α7 nicotinic receptor is a pentameric ligand-gated ion channel widely expressed in the central nervous system, where it plays key roles in cognition, attention, and memory. It is also found in non-neuronal cells, contributing to anti- inflammatory and neuroprotective processes. The enhancement of α7 activity is emerging as a promising therapeutic strategy for neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, as well as neurological and inflammatory conditions. Despite promising preclinical and clinical data, no α7- specific ligand has been approved for clinical use yet. Our objective is to elucidate the molecular function of α7 and its modulation under physiological and pathological conditions, in order to advance its potential as a therapeutic target. We expressed α7 in mammalian cells and assessed its function using single- channel and macroscopic current patch-clamp recordings. Through this approach, we identified natural and synthetic compounds that act as novel α7 positive allosteric modulators, exhibiting neuroprotective properties and offering new molecules with therapeutic potential. Additionally, we characterized new mechanisms of α7 modulation, including interactions with oligomeric amyloid beta peptides associated with Alzheimer's disease, cannabidiol, phosphorylation, calcium, and other nicotinic receptor subunits. These findings provide critical insights to be considered in future clinical trials. By investigating α7 function from a molecular perspective, our results lay the groundwork for its implementation as a viable therapeutic drug target. |
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2024 |
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2024 |
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http://hdl.handle.net/11336/251350 Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target; LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental; Bahía Blanca; Argentina; 2024; 19-19 CONICET Digital CONICET |
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Deciphering the molecular function of the α7 nicotinic receptor for its implementation as a clinical drug target; LVI Reunión Anual de la Asociación Argentina de Farmacología Experimental; Bahía Blanca; Argentina; 2024; 19-19 CONICET Digital CONICET |
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