Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease

Autores
Bruno, Martin; Leon, Wanda C.; Fragoso, Gabriela; Mushynski, Walter E.; Almazan, Guillermina; Cuello, A. Claudio
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have reported that the precursor form of nerve growth factor (proNGF) and not the mature NGF is liberated in the CNS in an activity-dependent manner and that its maturation and degradation occurs in the extracellular space by the coordinated action of proteases (Bruno & Cuello, 2006). In this report we communicate evidence for a diminished conversion of the NGF precursor molecule to its mature form as well as evidence for an increased NGF-degradation in Alzheimer’s brain samples. These alterations of the NGF metabolic pathway result in an up-regulation of proNGF levels. In these Alzheimer’s brain samples we have also found that the elevated proNGF occurs largely in a peroxynitrated form.  The intrahippocampal injection of Aß-oligomers provoked a similar up-regulation of proNGF in naïve rats, along with microglia activation, increased levels of inducible nitric oxide synthase (iNOS) and hyperactivity of the NGF degrading enzyme MMP-9. The elevated iNOS provoked the generation of biologically inactive; peroxynitrite-modified proNGF in Aß oligomer-injected rats.  These parameters were corrected with the application of minocycline.  The application of minocycline in a transgenic AD mouse model also diminished altered MMP-9, iNOS and microglial activation, preserving cognitive behavior and normalizing proNGF levels. These effects of Aß amyloid CNS burden on NGF metabolism would explain the well-known and paradoxical up-regulation of proNGF in Alzheimer disease, accompanying by atrophy of forebrain cholinergic neurons.
Fil: Bruno, Martin. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas. Departamento de Neurociencia; Argentina
Fil: Leon, Wanda C.. McGill University; Canadá
Fil: Fragoso, Gabriela. McGill University; Canadá
Fil: Mushynski, Walter E.. McGill University; Canadá
Fil: Almazan, Guillermina. McGill University; Canadá
Fil: Cuello, A. Claudio. McGill University; Canadá
Materia
Alzheimer disease
Abeta amyloid oligomers
Nerve growth factor
Peroxynitrite
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:11336/247879
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/247879
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer DiseaseBruno, MartinLeon, Wanda C.Fragoso, GabrielaMushynski, Walter E.Almazan, GuillerminaCuello, A. ClaudioAlzheimer diseaseAbeta amyloid oligomersNerve growth factorPeroxynitritehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have reported that the precursor form of nerve growth factor (proNGF) and not the mature NGF is liberated in the CNS in an activity-dependent manner and that its maturation and degradation occurs in the extracellular space by the coordinated action of proteases (Bruno & Cuello, 2006). In this report we communicate evidence for a diminished conversion of the NGF precursor molecule to its mature form as well as evidence for an increased NGF-degradation in Alzheimer’s brain samples. These alterations of the NGF metabolic pathway result in an up-regulation of proNGF levels. In these Alzheimer’s brain samples we have also found that the elevated proNGF occurs largely in a peroxynitrated form.  The intrahippocampal injection of Aß-oligomers provoked a similar up-regulation of proNGF in naïve rats, along with microglia activation, increased levels of inducible nitric oxide synthase (iNOS) and hyperactivity of the NGF degrading enzyme MMP-9. The elevated iNOS provoked the generation of biologically inactive; peroxynitrite-modified proNGF in Aß oligomer-injected rats.  These parameters were corrected with the application of minocycline.  The application of minocycline in a transgenic AD mouse model also diminished altered MMP-9, iNOS and microglial activation, preserving cognitive behavior and normalizing proNGF levels. These effects of Aß amyloid CNS burden on NGF metabolism would explain the well-known and paradoxical up-regulation of proNGF in Alzheimer disease, accompanying by atrophy of forebrain cholinergic neurons.Fil: Bruno, Martin. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas. Departamento de Neurociencia; ArgentinaFil: Leon, Wanda C.. McGill University; CanadáFil: Fragoso, Gabriela. McGill University; CanadáFil: Mushynski, Walter E.. McGill University; CanadáFil: Almazan, Guillermina. McGill University; CanadáFil: Cuello, A. Claudio. McGill University; CanadáLippincott Williams2009-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/247879Bruno, Martin; Leon, Wanda C.; Fragoso, Gabriela; Mushynski, Walter E.; Almazan, Guillermina; et al.; Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease; Lippincott Williams; Journal Of Neuropathology And Experimental Neurology; 68; 8; 8-2009; 857-8690022-3069CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jnen/article-abstract/68/8/857/2917078?redirectedFrom=PDFinfo:eu-repo/semantics/altIdentifier/doi/10.1097/NEN.0b013e3181aed9e6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:27:22Zoai:ri.conicet.gov.ar:11336/247879instacron: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:34982025-10-15 15:27:22.842CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
title Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
spellingShingle Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
Bruno, Martin
Alzheimer disease
Abeta amyloid oligomers
Nerve growth factor
Peroxynitrite
title_short Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
title_full Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
title_fullStr Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
title_full_unstemmed Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
title_sort Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
dc.creator.none.fl_str_mv Bruno, Martin
Leon, Wanda C.
Fragoso, Gabriela
Mushynski, Walter E.
Almazan, Guillermina
Cuello, A. Claudio
author Bruno, Martin
author_facet Bruno, Martin
Leon, Wanda C.
Fragoso, Gabriela
Mushynski, Walter E.
Almazan, Guillermina
Cuello, A. Claudio
author_role author
author2 Leon, Wanda C.
Fragoso, Gabriela
Mushynski, Walter E.
Almazan, Guillermina
Cuello, A. Claudio
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer disease
Abeta amyloid oligomers
Nerve growth factor
Peroxynitrite
topic Alzheimer disease
Abeta amyloid oligomers
Nerve growth factor
Peroxynitrite
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have reported that the precursor form of nerve growth factor (proNGF) and not the mature NGF is liberated in the CNS in an activity-dependent manner and that its maturation and degradation occurs in the extracellular space by the coordinated action of proteases (Bruno & Cuello, 2006). In this report we communicate evidence for a diminished conversion of the NGF precursor molecule to its mature form as well as evidence for an increased NGF-degradation in Alzheimer’s brain samples. These alterations of the NGF metabolic pathway result in an up-regulation of proNGF levels. In these Alzheimer’s brain samples we have also found that the elevated proNGF occurs largely in a peroxynitrated form.  The intrahippocampal injection of Aß-oligomers provoked a similar up-regulation of proNGF in naïve rats, along with microglia activation, increased levels of inducible nitric oxide synthase (iNOS) and hyperactivity of the NGF degrading enzyme MMP-9. The elevated iNOS provoked the generation of biologically inactive; peroxynitrite-modified proNGF in Aß oligomer-injected rats.  These parameters were corrected with the application of minocycline.  The application of minocycline in a transgenic AD mouse model also diminished altered MMP-9, iNOS and microglial activation, preserving cognitive behavior and normalizing proNGF levels. These effects of Aß amyloid CNS burden on NGF metabolism would explain the well-known and paradoxical up-regulation of proNGF in Alzheimer disease, accompanying by atrophy of forebrain cholinergic neurons.
Fil: Bruno, Martin. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas. Departamento de Neurociencia; Argentina
Fil: Leon, Wanda C.. McGill University; Canadá
Fil: Fragoso, Gabriela. McGill University; Canadá
Fil: Mushynski, Walter E.. McGill University; Canadá
Fil: Almazan, Guillermina. McGill University; Canadá
Fil: Cuello, A. Claudio. McGill University; Canadá
description We have reported that the precursor form of nerve growth factor (proNGF) and not the mature NGF is liberated in the CNS in an activity-dependent manner and that its maturation and degradation occurs in the extracellular space by the coordinated action of proteases (Bruno & Cuello, 2006). In this report we communicate evidence for a diminished conversion of the NGF precursor molecule to its mature form as well as evidence for an increased NGF-degradation in Alzheimer’s brain samples. These alterations of the NGF metabolic pathway result in an up-regulation of proNGF levels. In these Alzheimer’s brain samples we have also found that the elevated proNGF occurs largely in a peroxynitrated form.  The intrahippocampal injection of Aß-oligomers provoked a similar up-regulation of proNGF in naïve rats, along with microglia activation, increased levels of inducible nitric oxide synthase (iNOS) and hyperactivity of the NGF degrading enzyme MMP-9. The elevated iNOS provoked the generation of biologically inactive; peroxynitrite-modified proNGF in Aß oligomer-injected rats.  These parameters were corrected with the application of minocycline.  The application of minocycline in a transgenic AD mouse model also diminished altered MMP-9, iNOS and microglial activation, preserving cognitive behavior and normalizing proNGF levels. These effects of Aß amyloid CNS burden on NGF metabolism would explain the well-known and paradoxical up-regulation of proNGF in Alzheimer disease, accompanying by atrophy of forebrain cholinergic neurons.
publishDate 2009
dc.date.none.fl_str_mv 2009-08
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/11336/247879
Bruno, Martin; Leon, Wanda C.; Fragoso, Gabriela; Mushynski, Walter E.; Almazan, Guillermina; et al.; Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease; Lippincott Williams; Journal Of Neuropathology And Experimental Neurology; 68; 8; 8-2009; 857-869
0022-3069
CONICET Digital
CONICET
url http://hdl.handle.net/11336/247879
identifier_str_mv Bruno, Martin; Leon, Wanda C.; Fragoso, Gabriela; Mushynski, Walter E.; Almazan, Guillermina; et al.; Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease; Lippincott Williams; Journal Of Neuropathology And Experimental Neurology; 68; 8; 8-2009; 857-869
0022-3069
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://academic.oup.com/jnen/article-abstract/68/8/857/2917078?redirectedFrom=PDF
info:eu-repo/semantics/altIdentifier/doi/10.1097/NEN.0b013e3181aed9e6
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
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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_ 1846083415925850112
score 13.22299

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