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dc.contributor.author
Allard, Simon  
dc.contributor.author
León, Wanda C.  
dc.contributor.author
Pakavathkumar, Prateep  
dc.contributor.author
Bruno, Martin  
dc.contributor.author
Ribeiro da Silva, Alfredo  
dc.contributor.author
Cuello, A. Claudio  
dc.date.available
2022-05-26T13:40:42Z  
dc.date.issued
2012-02  
dc.identifier.citation
Allard, Simon; León, Wanda C.; Pakavathkumar, Prateep; Bruno, Martin; Ribeiro da Silva, Alfredo; et al.; Impact of the NGF Maturation and Degradation Pathway on the Cortical Cholinergic System Phenotype; Society for Neuroscience; Journal of Neuroscience; 32; 6; 2-2012; 2002-2012  
dc.identifier.issn
0270-6474  
dc.identifier.uri
http://hdl.handle.net/11336/158228  
dc.description.abstract
Cortical cholinergic atrophy plays a significant role in the cognitive loss seen with aging and in Alzheimer's disease (AD), but the mechanisms leading to it remain unresolved. Nerve growth factor (NGF) is the neurotrophin responsible for the phenotypic maintenance of basal forebrain cholinergic neurons in the mature and fully differentiated CNS. In consequence, its implication in cholinergic atrophy has been suspected; however, no mechanistic explanation has been provided. We have previously shown that the precursor of NGF (proNGF) is cleaved extracellularly by plasmin to form mature NGF (mNGF) and that mNGF is degraded by matrix metalloproteinase 9. Using cognitive-behavioral tests, Western blotting, and confocal and electron microscopy, this study demonstrates that a pharmacologically induced chronic failure in extracellular NGF maturation leads to a reduction in mNGF levels, proNGF accumulation, cholinergic degeneration, and cognitive impairment in rats. It also shows that inhibiting NGF degradation increases endogenous levels of the mature neurotrophin and increases the density of cortical cholinergic boutons. Together, the data point to a mechanism explaining cholinergic loss in neurodegenerative conditions such as AD and provide a potential therapeutic target for the protection or restoration of this CNS transmitter system in aging and AD.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Society for Neuroscience  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/  
dc.subject
FACTOR DE CRECIMIENTO NERVIOSO (NGF)  
dc.subject
MATRIX METALOPROTEINASA 9 (MMP-9)  
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PLASMINA  
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SISTEMA COLINÉRGICO  
dc.subject.classification
Neurociencias  
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Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Impact of the NGF Maturation and Degradation Pathway on the Cortical Cholinergic System Phenotype  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2022-05-20T14:05:30Z  
dc.journal.volume
32  
dc.journal.number
6  
dc.journal.pagination
2002-2012  
dc.journal.pais
Estados Unidos  
dc.journal.ciudad
Washington  
dc.description.fil
Fil: Allard, Simon. McGill University. Department of Pharmacology and Therapeutics; Canadá  
dc.description.fil
Fil: León, Wanda C.. McGill University. Department of Pharmacology and Therapeutics; Canadá  
dc.description.fil
Fil: Pakavathkumar, Prateep. McGill University. Department of Pharmacology and Therapeutics; Canadá  
dc.description.fil
Fil: Bruno, Martin. 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: Ribeiro da Silva, Alfredo. McGill University; Canadá  
dc.description.fil
Fil: Cuello, A. Claudio. McGill University; Canadá  
dc.journal.title
Journal of Neuroscience  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1523/JNEUROSCI.1144-11.2012  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.jneurosci.org/content/32/6/2002