Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis

Autores
Silva, Berenice Anabel; Leal, Maria Celeste; Farias, Maria Isabel; Nava, Agustín; Galván, Daniela Inés; Fernandez, Elmer Andres; Pitossi, Fernando Juan; Ferrari, Carina Cintia
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction: Multiple Sclerosis (MS) is a complex neurodegenerative diseasemarked by recurring inflammatory episodes, demyelination, axonal damage, andsubsequent loss of function. MS presents a wide range of clinical courses, withthe progressive forms leading to irreversible neurological disability. Corticaldemyelinating lesions are central to the pathology of these progressive forms,gaining critical importance in recent decades due to their strong correlation withphysical disability and cognitive decline. Despite this, the underlying mechanismsdriving cortical lesion formation remain poorly understood, and no specifictreatments are currently available. A significant challenge lies in the lack ofanimal models that accurately mirror the key characteristics of these lesions.Methods: We developed a focal cortical animal model that replicates manyfeatures of cortical lesions, including cognitive impairment. This study focuses onconducting proteomic analyses of both the cortical lesions and cerebrospinalfluid (CSF) from these animals, aiming to identify key proteins and biomarkers thatcould be validated in MS patients.Results: Proteomic differences between frontal cortex tissue and CSF wereobserved when comparing experimental animals with controls. Among theidentified proteins, some have been previously described in MS patients andanimal models, while others represent novel discoveries. Notably, we identifiedtwo proteins, S100A8 and orosomucoid-1, that were highly expressed inboth regions.Conclusions: These findings suggest that the prognostic molecules identified inthis model could facilitate the discovery of new biomarkers or key moleculesrelevant to MS, particularly in the cortical lesion that mainly characterized theprogressive forms of the disease.
Fil: Silva, Berenice Anabel. 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: Leal, Maria Celeste. 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: Farias, Maria Isabel. 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: Nava, Agustín. 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: Galván, Daniela Inés. 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: Fernandez, Elmer Andres. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Pitossi, Fernando Juan. 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: Ferrari, Carina Cintia. 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
Materia
CORTEX
CSF
DEMYELINATION
NEURODEGENERATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/275157
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/275157
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosisSilva, Berenice AnabelLeal, Maria CelesteFarias, Maria IsabelNava, AgustínGalván, Daniela InésFernandez, Elmer AndresPitossi, Fernando JuanFerrari, Carina CintiaCORTEXCSFDEMYELINATIONNEURODEGENERATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Introduction: Multiple Sclerosis (MS) is a complex neurodegenerative diseasemarked by recurring inflammatory episodes, demyelination, axonal damage, andsubsequent loss of function. MS presents a wide range of clinical courses, withthe progressive forms leading to irreversible neurological disability. Corticaldemyelinating lesions are central to the pathology of these progressive forms,gaining critical importance in recent decades due to their strong correlation withphysical disability and cognitive decline. Despite this, the underlying mechanismsdriving cortical lesion formation remain poorly understood, and no specifictreatments are currently available. A significant challenge lies in the lack ofanimal models that accurately mirror the key characteristics of these lesions.Methods: We developed a focal cortical animal model that replicates manyfeatures of cortical lesions, including cognitive impairment. This study focuses onconducting proteomic analyses of both the cortical lesions and cerebrospinalfluid (CSF) from these animals, aiming to identify key proteins and biomarkers thatcould be validated in MS patients.Results: Proteomic differences between frontal cortex tissue and CSF wereobserved when comparing experimental animals with controls. Among theidentified proteins, some have been previously described in MS patients andanimal models, while others represent novel discoveries. Notably, we identifiedtwo proteins, S100A8 and orosomucoid-1, that were highly expressed inboth regions.Conclusions: These findings suggest that the prognostic molecules identified inthis model could facilitate the discovery of new biomarkers or key moleculesrelevant to MS, particularly in the cortical lesion that mainly characterized theprogressive forms of the disease.Fil: Silva, Berenice Anabel. 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: Leal, Maria Celeste. 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: Farias, Maria Isabel. 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: Nava, Agustín. 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: Galván, Daniela Inés. 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: Fernandez, Elmer Andres. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Pitossi, Fernando Juan. 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: Ferrari, Carina Cintia. 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; ArgentinaFrontiers Media2025-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/275157Silva, Berenice Anabel; Leal, Maria Celeste; Farias, Maria Isabel; Nava, Agustín; Galván, Daniela Inés; et al.; Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis; Frontiers Media; Frontiers in Immunology; 16; 2-2025; 1-201664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2025.1505459/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2025.1505459info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-17T14:17:53Zoai:ri.conicet.gov.ar:11336/275157instacron: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:34982025-12-17 14:17:53.323CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
title Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
spellingShingle Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
Silva, Berenice Anabel
CORTEX
CSF
DEMYELINATION
NEURODEGENERATION
title_short Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
title_full Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
title_fullStr Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
title_full_unstemmed Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
title_sort Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis
dc.creator.none.fl_str_mv Silva, Berenice Anabel
Leal, Maria Celeste
Farias, Maria Isabel
Nava, Agustín
Galván, Daniela Inés
Fernandez, Elmer Andres
Pitossi, Fernando Juan
Ferrari, Carina Cintia
author Silva, Berenice Anabel
author_facet Silva, Berenice Anabel
Leal, Maria Celeste
Farias, Maria Isabel
Nava, Agustín
Galván, Daniela Inés
Fernandez, Elmer Andres
Pitossi, Fernando Juan
Ferrari, Carina Cintia
author_role author
author2 Leal, Maria Celeste
Farias, Maria Isabel
Nava, Agustín
Galván, Daniela Inés
Fernandez, Elmer Andres
Pitossi, Fernando Juan
Ferrari, Carina Cintia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CORTEX
CSF
DEMYELINATION
NEURODEGENERATION
topic CORTEX
CSF
DEMYELINATION
NEURODEGENERATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Introduction: Multiple Sclerosis (MS) is a complex neurodegenerative diseasemarked by recurring inflammatory episodes, demyelination, axonal damage, andsubsequent loss of function. MS presents a wide range of clinical courses, withthe progressive forms leading to irreversible neurological disability. Corticaldemyelinating lesions are central to the pathology of these progressive forms,gaining critical importance in recent decades due to their strong correlation withphysical disability and cognitive decline. Despite this, the underlying mechanismsdriving cortical lesion formation remain poorly understood, and no specifictreatments are currently available. A significant challenge lies in the lack ofanimal models that accurately mirror the key characteristics of these lesions.Methods: We developed a focal cortical animal model that replicates manyfeatures of cortical lesions, including cognitive impairment. This study focuses onconducting proteomic analyses of both the cortical lesions and cerebrospinalfluid (CSF) from these animals, aiming to identify key proteins and biomarkers thatcould be validated in MS patients.Results: Proteomic differences between frontal cortex tissue and CSF wereobserved when comparing experimental animals with controls. Among theidentified proteins, some have been previously described in MS patients andanimal models, while others represent novel discoveries. Notably, we identifiedtwo proteins, S100A8 and orosomucoid-1, that were highly expressed inboth regions.Conclusions: These findings suggest that the prognostic molecules identified inthis model could facilitate the discovery of new biomarkers or key moleculesrelevant to MS, particularly in the cortical lesion that mainly characterized theprogressive forms of the disease.
Fil: Silva, Berenice Anabel. 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: Leal, Maria Celeste. 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: Farias, Maria Isabel. 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: Nava, Agustín. 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: Galván, Daniela Inés. 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: Fernandez, Elmer Andres. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Pitossi, Fernando Juan. 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: Ferrari, Carina Cintia. 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
description Introduction: Multiple Sclerosis (MS) is a complex neurodegenerative diseasemarked by recurring inflammatory episodes, demyelination, axonal damage, andsubsequent loss of function. MS presents a wide range of clinical courses, withthe progressive forms leading to irreversible neurological disability. Corticaldemyelinating lesions are central to the pathology of these progressive forms,gaining critical importance in recent decades due to their strong correlation withphysical disability and cognitive decline. Despite this, the underlying mechanismsdriving cortical lesion formation remain poorly understood, and no specifictreatments are currently available. A significant challenge lies in the lack ofanimal models that accurately mirror the key characteristics of these lesions.Methods: We developed a focal cortical animal model that replicates manyfeatures of cortical lesions, including cognitive impairment. This study focuses onconducting proteomic analyses of both the cortical lesions and cerebrospinalfluid (CSF) from these animals, aiming to identify key proteins and biomarkers thatcould be validated in MS patients.Results: Proteomic differences between frontal cortex tissue and CSF wereobserved when comparing experimental animals with controls. Among theidentified proteins, some have been previously described in MS patients andanimal models, while others represent novel discoveries. Notably, we identifiedtwo proteins, S100A8 and orosomucoid-1, that were highly expressed inboth regions.Conclusions: These findings suggest that the prognostic molecules identified inthis model could facilitate the discovery of new biomarkers or key moleculesrelevant to MS, particularly in the cortical lesion that mainly characterized theprogressive forms of the disease.
publishDate 2025
dc.date.none.fl_str_mv 2025-02
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/11336/275157
Silva, Berenice Anabel; Leal, Maria Celeste; Farias, Maria Isabel; Nava, Agustín; Galván, Daniela Inés; et al.; Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis; Frontiers Media; Frontiers in Immunology; 16; 2-2025; 1-20
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/275157
identifier_str_mv Silva, Berenice Anabel; Leal, Maria Celeste; Farias, Maria Isabel; Nava, Agustín; Galván, Daniela Inés; et al.; Proteomic analysis reveals candidate molecules to mediate cortical pathology and identify possible biomarkers in an animal model of multiple sclerosis; Frontiers Media; Frontiers in Immunology; 16; 2-2025; 1-20
1664-3224
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.frontiersin.org/articles/10.3389/fimmu.2025.1505459/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2025.1505459
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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