Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.

Autores
Valles, Ana Sofia; Borroni, Maria Virginia; Barrantes, Francisco Jose
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alzheimer´s disease (AD) is the most common form of dementia among older persons. Pathognomonic hallmarks of the disease include the development of amyloid senile plaques and deposits of neurofibrillary tangles. These changes occur in the brain long before the clinical manifestations of AD (cognitive impairment in particular) become apparent. Nicotinic acetylcholine receptors (AChRs), particularly the α7 subtype, are highly expressed in brain regions relevant to cognitive and memory functions and involved in the processing of sensory information. There is strong evidence that implicates the participation of AChRs in AD. This review briefly introduces current strategies addressing the pathophysiologic findings (amyloid-β-peptide plaques, neurofibrillary tangles) and then focuses on more recent efforts of pharmacologic intervention in AD, specifically targeted to the α7 AChR. Whereas cholinesterase inhibitors such as donepezil, galantamine, or rivastigmine, together with the non-competitive N-methyl-D-aspartate receptor antagonist memantine are at the forefront of present-day clinical intervention for AD, new insights into AChR molecular pharmacology are bringing other drugs, directed at AChRs, to center stage. Among these are the positive allosteric modulators that selectively target α7 AChRs and are aimed at unleashing the factors that hinder agonist-mediated, α7 AChR channel activation. This calls for more detailed knowledge of the distribution, functional properties, and involvement of AChRs in various signaling cascades-together with the corresponding abnormalities in all these properties-to be able to engineer strategies in drug design and evaluate the therapeutic possibilities of new compounds targeting this class of neurotransmitter receptors.
Fil: Valles, Ana Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Borroni, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina
Materia
Achr
Alzheimer
Agonist
Drugs
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4547
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4547
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.Valles, Ana SofiaBorroni, Maria VirginiaBarrantes, Francisco JoseAchrAlzheimerAgonistDrugshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Alzheimer´s disease (AD) is the most common form of dementia among older persons. Pathognomonic hallmarks of the disease include the development of amyloid senile plaques and deposits of neurofibrillary tangles. These changes occur in the brain long before the clinical manifestations of AD (cognitive impairment in particular) become apparent. Nicotinic acetylcholine receptors (AChRs), particularly the α7 subtype, are highly expressed in brain regions relevant to cognitive and memory functions and involved in the processing of sensory information. There is strong evidence that implicates the participation of AChRs in AD. This review briefly introduces current strategies addressing the pathophysiologic findings (amyloid-β-peptide plaques, neurofibrillary tangles) and then focuses on more recent efforts of pharmacologic intervention in AD, specifically targeted to the α7 AChR. Whereas cholinesterase inhibitors such as donepezil, galantamine, or rivastigmine, together with the non-competitive N-methyl-D-aspartate receptor antagonist memantine are at the forefront of present-day clinical intervention for AD, new insights into AChR molecular pharmacology are bringing other drugs, directed at AChRs, to center stage. Among these are the positive allosteric modulators that selectively target α7 AChRs and are aimed at unleashing the factors that hinder agonist-mediated, α7 AChR channel activation. This calls for more detailed knowledge of the distribution, functional properties, and involvement of AChRs in various signaling cascades-together with the corresponding abnormalities in all these properties-to be able to engineer strategies in drug design and evaluate the therapeutic possibilities of new compounds targeting this class of neurotransmitter receptors.Fil: Valles, Ana Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Borroni, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaAdis Int Ltd2014-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4547Valles, Ana Sofia; Borroni, Maria Virginia; Barrantes, Francisco Jose; Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.; Adis Int Ltd; Cns Drugs; 11-20141172-7047enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1007/s40263-014-0201-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:45Zoai:ri.conicet.gov.ar:11336/4547instacron: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 09:59:45.357CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
title Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
spellingShingle Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
Valles, Ana Sofia
Achr
Alzheimer
Agonist
Drugs
title_short Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
title_full Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
title_fullStr Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
title_full_unstemmed Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
title_sort Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.
dc.creator.none.fl_str_mv Valles, Ana Sofia
Borroni, Maria Virginia
Barrantes, Francisco Jose
author Valles, Ana Sofia
author_facet Valles, Ana Sofia
Borroni, Maria Virginia
Barrantes, Francisco Jose
author_role author
author2 Borroni, Maria Virginia
Barrantes, Francisco Jose
author2_role author
author
dc.subject.none.fl_str_mv Achr
Alzheimer
Agonist
Drugs
topic Achr
Alzheimer
Agonist
Drugs
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alzheimer´s disease (AD) is the most common form of dementia among older persons. Pathognomonic hallmarks of the disease include the development of amyloid senile plaques and deposits of neurofibrillary tangles. These changes occur in the brain long before the clinical manifestations of AD (cognitive impairment in particular) become apparent. Nicotinic acetylcholine receptors (AChRs), particularly the α7 subtype, are highly expressed in brain regions relevant to cognitive and memory functions and involved in the processing of sensory information. There is strong evidence that implicates the participation of AChRs in AD. This review briefly introduces current strategies addressing the pathophysiologic findings (amyloid-β-peptide plaques, neurofibrillary tangles) and then focuses on more recent efforts of pharmacologic intervention in AD, specifically targeted to the α7 AChR. Whereas cholinesterase inhibitors such as donepezil, galantamine, or rivastigmine, together with the non-competitive N-methyl-D-aspartate receptor antagonist memantine are at the forefront of present-day clinical intervention for AD, new insights into AChR molecular pharmacology are bringing other drugs, directed at AChRs, to center stage. Among these are the positive allosteric modulators that selectively target α7 AChRs and are aimed at unleashing the factors that hinder agonist-mediated, α7 AChR channel activation. This calls for more detailed knowledge of the distribution, functional properties, and involvement of AChRs in various signaling cascades-together with the corresponding abnormalities in all these properties-to be able to engineer strategies in drug design and evaluate the therapeutic possibilities of new compounds targeting this class of neurotransmitter receptors.
Fil: Valles, Ana Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Borroni, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Barrantes, Francisco Jose. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina
description Alzheimer´s disease (AD) is the most common form of dementia among older persons. Pathognomonic hallmarks of the disease include the development of amyloid senile plaques and deposits of neurofibrillary tangles. These changes occur in the brain long before the clinical manifestations of AD (cognitive impairment in particular) become apparent. Nicotinic acetylcholine receptors (AChRs), particularly the α7 subtype, are highly expressed in brain regions relevant to cognitive and memory functions and involved in the processing of sensory information. There is strong evidence that implicates the participation of AChRs in AD. This review briefly introduces current strategies addressing the pathophysiologic findings (amyloid-β-peptide plaques, neurofibrillary tangles) and then focuses on more recent efforts of pharmacologic intervention in AD, specifically targeted to the α7 AChR. Whereas cholinesterase inhibitors such as donepezil, galantamine, or rivastigmine, together with the non-competitive N-methyl-D-aspartate receptor antagonist memantine are at the forefront of present-day clinical intervention for AD, new insights into AChR molecular pharmacology are bringing other drugs, directed at AChRs, to center stage. Among these are the positive allosteric modulators that selectively target α7 AChRs and are aimed at unleashing the factors that hinder agonist-mediated, α7 AChR channel activation. This calls for more detailed knowledge of the distribution, functional properties, and involvement of AChRs in various signaling cascades-together with the corresponding abnormalities in all these properties-to be able to engineer strategies in drug design and evaluate the therapeutic possibilities of new compounds targeting this class of neurotransmitter receptors.
publishDate 2014
dc.date.none.fl_str_mv 2014-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/4547
Valles, Ana Sofia; Borroni, Maria Virginia; Barrantes, Francisco Jose; Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.; Adis Int Ltd; Cns Drugs; 11-2014
1172-7047
url http://hdl.handle.net/11336/4547
identifier_str_mv Valles, Ana Sofia; Borroni, Maria Virginia; Barrantes, Francisco Jose; Targeting Brain alpha;7 Nicotinic Acetylcholine Receptors in Alzheimer's Disease: Rationale and Current Status.; Adis Int Ltd; Cns Drugs; 11-2014
1172-7047
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1007/s40263-014-0201-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Adis Int Ltd
publisher.none.fl_str_mv Adis Int Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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 13.13397

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