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dc.contributor.author
Bruno, Martin  
dc.contributor.author
Leon, Wanda C.  
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Fragoso, Gabriela  
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Mushynski, Walter E.  
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Almazan, Guillermina  
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Cuello, A. Claudio  
dc.date.available
2024-11-11T16:01:50Z  
dc.date.issued
2009-08  
dc.identifier.citation
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  
dc.identifier.issn
0022-3069  
dc.identifier.uri
http://hdl.handle.net/11336/247879  
dc.description.abstract
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.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Lippincott Williams  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Alzheimer disease  
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Abeta amyloid oligomers  
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Nerve growth factor  
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Peroxynitrite  
dc.subject.classification
Neurociencias  
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Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Amyloid β-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2024-11-11T14:37:27Z  
dc.journal.volume
68  
dc.journal.number
8  
dc.journal.pagination
857-869  
dc.journal.pais
Estados Unidos  
dc.description.fil
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  
dc.description.fil
Fil: Leon, Wanda C.. McGill University; Canadá  
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Fil: Fragoso, Gabriela. McGill University; Canadá  
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Fil: Mushynski, Walter E.. McGill University; Canadá  
dc.description.fil
Fil: Almazan, Guillermina. McGill University; Canadá  
dc.description.fil
Fil: Cuello, A. Claudio. McGill University; Canadá  
dc.journal.title
Journal Of Neuropathology And Experimental Neurology  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/jnen/article-abstract/68/8/857/2917078?redirectedFrom=PDF  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1097/NEN.0b013e3181aed9e6