Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis

Autores
Medina Vera, Dina; López Gambero, Antonio J.; Verheul, Julia; Navarro, Juan A.; Morelli, Laura; Galeano, Pablo; Suárez, Juan; Sanjuan, Carlos; Pacheco Sánchez, Beatriz; Rivera, Patricia; Pavon Morón, Francisco J.; Rosell Valle, Cristina; Fonseca, Fernando Rodríguez de
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background. Objectives, Alzheimers disease (AD), a leading cause of dementia, lacks effective long term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Abeta) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut. Given this context, exploring alternative therapeutic interventions capable of addressing the multifaceted components of AD etiology is essential. Methods, this study suggests dPinitol (DPIN) as a potential treatment modifier for AD. DPIN, derived from carob pods, demonstrates insulin sensitizing, tau hyperphosphorylation inhibition, and antioxidant properties. To test this hypothesis, we studied whether chronic oral administration of DPIN (200 mg kg day) could reverse the AD like disease progression in the 5XFAD mice. Results, results showed that treatment of 5XFAD mice with DPIN improved cognition, reduced hippocampal Abeta and hyperphosphorylated tau levels, increased insulin degrading enzyme (IDE) expression, enhanced procognitive hormone circulation (such as ghrelin and leptin), and normalized the PI3K Akt insulin pathway. This enhancement may be mediated through the modulation of cyclin dependent kinase 5 (CDK5). DPIN also protected the gut barrier and microbiota, reducing the proinflammatory impact of the leaky gut observed in 5XFAD mice. DPIN reduced bacterial lipopolysaccharide (LPS) and LPS associated inflammation, as well as restored intestinal proteins such as Claudin3. This effect was associated with a modulation of gut microbiota towards a more balanced bacterial composition. Conclusions, these findings underscore DPINs promise in mitigating cognitive decline in the early AD stages, positioning it as a potential disease modifier.
Fil: Medina Vera, Dina. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: López Gambero, Antonio J.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Verheul, Julia. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Navarro, Juan A.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Suárez, Juan. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Sanjuan, Carlos. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Pacheco Sánchez, Beatriz. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Rivera, Patricia. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Pavon Morón, Francisco J.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Rosell Valle, Cristina. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Fonseca, Fernando Rodríguez de. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Materia
ALZHEIMERS DISEASE
BRAIN INSULIN RESISTANCE
HIPPOCAMPUS
ABETA PLAQUES
CDK5
MICROBIOTA DYSBIOSIS
TAU PHOSPHORYLATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266239
Acceder
id CONICETDig_6846b81fadba83a103606461d670ebf4
oai_identifier_str oai:ri.conicet.gov.ar:11336/266239
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s AmyloidosisMedina Vera, DinaLópez Gambero, Antonio J.Verheul, JuliaNavarro, Juan A.Morelli, LauraGaleano, PabloSuárez, JuanSanjuan, CarlosPacheco Sánchez, BeatrizRivera, PatriciaPavon Morón, Francisco J.Rosell Valle, CristinaFonseca, Fernando Rodríguez deALZHEIMERS DISEASEBRAIN INSULIN RESISTANCEHIPPOCAMPUSABETA PLAQUESCDK5MICROBIOTA DYSBIOSISTAU PHOSPHORYLATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background. Objectives, Alzheimers disease (AD), a leading cause of dementia, lacks effective long term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Abeta) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut. Given this context, exploring alternative therapeutic interventions capable of addressing the multifaceted components of AD etiology is essential. Methods, this study suggests dPinitol (DPIN) as a potential treatment modifier for AD. DPIN, derived from carob pods, demonstrates insulin sensitizing, tau hyperphosphorylation inhibition, and antioxidant properties. To test this hypothesis, we studied whether chronic oral administration of DPIN (200 mg kg day) could reverse the AD like disease progression in the 5XFAD mice. Results, results showed that treatment of 5XFAD mice with DPIN improved cognition, reduced hippocampal Abeta and hyperphosphorylated tau levels, increased insulin degrading enzyme (IDE) expression, enhanced procognitive hormone circulation (such as ghrelin and leptin), and normalized the PI3K Akt insulin pathway. This enhancement may be mediated through the modulation of cyclin dependent kinase 5 (CDK5). DPIN also protected the gut barrier and microbiota, reducing the proinflammatory impact of the leaky gut observed in 5XFAD mice. DPIN reduced bacterial lipopolysaccharide (LPS) and LPS associated inflammation, as well as restored intestinal proteins such as Claudin3. This effect was associated with a modulation of gut microbiota towards a more balanced bacterial composition. Conclusions, these findings underscore DPINs promise in mitigating cognitive decline in the early AD stages, positioning it as a potential disease modifier.Fil: Medina Vera, Dina. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: López Gambero, Antonio J.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Verheul, Julia. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Navarro, Juan A.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Suárez, Juan. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Sanjuan, Carlos. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Pacheco Sánchez, Beatriz. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Rivera, Patricia. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Pavon Morón, Francisco J.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Rosell Valle, Cristina. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaFil: Fonseca, Fernando Rodríguez de. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; EspañaMultidisciplinary Digital Publishing Institute2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266239Medina Vera, Dina; López Gambero, Antonio J.; Verheul, Julia; Navarro, Juan A.; Morelli, Laura; et al.; Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis; Multidisciplinary Digital Publishing Institute; Nutrients; 16; 23; 12-2024; 1-262072-6643CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6643/16/23/4186info:eu-repo/semantics/altIdentifier/doi/10.3390/nu16234186info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:42:21Zoai:ri.conicet.gov.ar:11336/266239instacron: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:34982025-10-22 11:42:22.11CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
title Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
spellingShingle Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
Medina Vera, Dina
ALZHEIMERS DISEASE
BRAIN INSULIN RESISTANCE
HIPPOCAMPUS
ABETA PLAQUES
CDK5
MICROBIOTA DYSBIOSIS
TAU PHOSPHORYLATION
title_short Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
title_full Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
title_fullStr Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
title_full_unstemmed Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
title_sort Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis
dc.creator.none.fl_str_mv Medina Vera, Dina
López Gambero, Antonio J.
Verheul, Julia
Navarro, Juan A.
Morelli, Laura
Galeano, Pablo
Suárez, Juan
Sanjuan, Carlos
Pacheco Sánchez, Beatriz
Rivera, Patricia
Pavon Morón, Francisco J.
Rosell Valle, Cristina
Fonseca, Fernando Rodríguez de
author Medina Vera, Dina
author_facet Medina Vera, Dina
López Gambero, Antonio J.
Verheul, Julia
Navarro, Juan A.
Morelli, Laura
Galeano, Pablo
Suárez, Juan
Sanjuan, Carlos
Pacheco Sánchez, Beatriz
Rivera, Patricia
Pavon Morón, Francisco J.
Rosell Valle, Cristina
Fonseca, Fernando Rodríguez de
author_role author
author2 López Gambero, Antonio J.
Verheul, Julia
Navarro, Juan A.
Morelli, Laura
Galeano, Pablo
Suárez, Juan
Sanjuan, Carlos
Pacheco Sánchez, Beatriz
Rivera, Patricia
Pavon Morón, Francisco J.
Rosell Valle, Cristina
Fonseca, Fernando Rodríguez de
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALZHEIMERS DISEASE
BRAIN INSULIN RESISTANCE
HIPPOCAMPUS
ABETA PLAQUES
CDK5
MICROBIOTA DYSBIOSIS
TAU PHOSPHORYLATION
topic ALZHEIMERS DISEASE
BRAIN INSULIN RESISTANCE
HIPPOCAMPUS
ABETA PLAQUES
CDK5
MICROBIOTA DYSBIOSIS
TAU PHOSPHORYLATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background. Objectives, Alzheimers disease (AD), a leading cause of dementia, lacks effective long term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Abeta) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut. Given this context, exploring alternative therapeutic interventions capable of addressing the multifaceted components of AD etiology is essential. Methods, this study suggests dPinitol (DPIN) as a potential treatment modifier for AD. DPIN, derived from carob pods, demonstrates insulin sensitizing, tau hyperphosphorylation inhibition, and antioxidant properties. To test this hypothesis, we studied whether chronic oral administration of DPIN (200 mg kg day) could reverse the AD like disease progression in the 5XFAD mice. Results, results showed that treatment of 5XFAD mice with DPIN improved cognition, reduced hippocampal Abeta and hyperphosphorylated tau levels, increased insulin degrading enzyme (IDE) expression, enhanced procognitive hormone circulation (such as ghrelin and leptin), and normalized the PI3K Akt insulin pathway. This enhancement may be mediated through the modulation of cyclin dependent kinase 5 (CDK5). DPIN also protected the gut barrier and microbiota, reducing the proinflammatory impact of the leaky gut observed in 5XFAD mice. DPIN reduced bacterial lipopolysaccharide (LPS) and LPS associated inflammation, as well as restored intestinal proteins such as Claudin3. This effect was associated with a modulation of gut microbiota towards a more balanced bacterial composition. Conclusions, these findings underscore DPINs promise in mitigating cognitive decline in the early AD stages, positioning it as a potential disease modifier.
Fil: Medina Vera, Dina. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: López Gambero, Antonio J.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Verheul, Julia. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Navarro, Juan A.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Suárez, Juan. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Sanjuan, Carlos. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Pacheco Sánchez, Beatriz. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Rivera, Patricia. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Pavon Morón, Francisco J.. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Rosell Valle, Cristina. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
Fil: Fonseca, Fernando Rodríguez de. Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina; España
description Background. Objectives, Alzheimers disease (AD), a leading cause of dementia, lacks effective long term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Abeta) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut. Given this context, exploring alternative therapeutic interventions capable of addressing the multifaceted components of AD etiology is essential. Methods, this study suggests dPinitol (DPIN) as a potential treatment modifier for AD. DPIN, derived from carob pods, demonstrates insulin sensitizing, tau hyperphosphorylation inhibition, and antioxidant properties. To test this hypothesis, we studied whether chronic oral administration of DPIN (200 mg kg day) could reverse the AD like disease progression in the 5XFAD mice. Results, results showed that treatment of 5XFAD mice with DPIN improved cognition, reduced hippocampal Abeta and hyperphosphorylated tau levels, increased insulin degrading enzyme (IDE) expression, enhanced procognitive hormone circulation (such as ghrelin and leptin), and normalized the PI3K Akt insulin pathway. This enhancement may be mediated through the modulation of cyclin dependent kinase 5 (CDK5). DPIN also protected the gut barrier and microbiota, reducing the proinflammatory impact of the leaky gut observed in 5XFAD mice. DPIN reduced bacterial lipopolysaccharide (LPS) and LPS associated inflammation, as well as restored intestinal proteins such as Claudin3. This effect was associated with a modulation of gut microbiota towards a more balanced bacterial composition. Conclusions, these findings underscore DPINs promise in mitigating cognitive decline in the early AD stages, positioning it as a potential disease modifier.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
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/11336/266239
Medina Vera, Dina; López Gambero, Antonio J.; Verheul, Julia; Navarro, Juan A.; Morelli, Laura; et al.; Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis; Multidisciplinary Digital Publishing Institute; Nutrients; 16; 23; 12-2024; 1-26
2072-6643
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266239
identifier_str_mv Medina Vera, Dina; López Gambero, Antonio J.; Verheul, Julia; Navarro, Juan A.; Morelli, Laura; et al.; Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer’s Amyloidosis; Multidisciplinary Digital Publishing Institute; Nutrients; 16; 23; 12-2024; 1-26
2072-6643
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://www.mdpi.com/2072-6643/16/23/4186
info:eu-repo/semantics/altIdentifier/doi/10.3390/nu16234186
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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
_version_ 1846782109961682944
score 12.982451

Publicaciones similares