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dc.contributor.author
Akhtar, Mohd Waseem  
dc.contributor.author
Sanz Blasco, Sara Isabel  
dc.contributor.author
Dolatabadi, Nima  
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Parker, James  
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Chon, Kevin  
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Lee, Michelle S.  
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Soussou, Walid  
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McKercher, Scott R.  
dc.contributor.author
Ambasudhan, Rajesh  
dc.contributor.author
Nakamura, Tomohiro  
dc.contributor.author
Lipton, Stuart A.  
dc.date.available
2018-03-19T21:50:20Z  
dc.date.issued
2016-01  
dc.identifier.citation
Akhtar, Mohd Waseem; Sanz Blasco, Sara Isabel; Dolatabadi, Nima; Parker, James; Chon, Kevin; et al.; Elevated glucose and oligomeric β-amyloid disrupt synapses via a common pathway of aberrant protein S-nitrosylation; Nature Publishing Group; Nature Communications; 7; 1024; 1-2016; 1-11  
dc.identifier.issn
2041-1723  
dc.identifier.uri
http://hdl.handle.net/11336/39318  
dc.description.abstract
Metabolic syndrome (MetS) and Type 2 diabetes mellitus (T2DM) increase risk for Alzheimerâ €™ s disease (AD). The molecular mechanism for this association remains poorly defined. Here we report in human and rodent tissues that elevated glucose, as found in MetS/T2DM, and oligomeric β-amyloid (Aβ) peptide, thought to be a key mediator of AD, coordinately increase neuronal Ca 2+ and nitric oxide (NO) in an NMDA receptor-dependent manner. The increase in NO results in S-nitrosylation of insulin-degrading enzyme (IDE) and dynamin-related protein 1 (Drp1), thus inhibiting insulin and Aβ catabolism as well as hyperactivating mitochondrial fission machinery. Consequent elevation in Aβ levels and compromise in mitochondrial bioenergetics result in dysfunctional synaptic plasticity and synapse loss in cortical and hippocampal neurons. The NMDA receptor antagonist memantine attenuates these effects. Our studies show that redox-mediated posttranslational modification of brain proteins link Aβ and hyperglycaemia to cognitive dysfunction in MetS/T2DM and AD.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Nature Publishing Group  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/  
dc.subject
Alzheimer  
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No  
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Nmda  
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Β-Amyloid (Aβ) Peptide  
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Glucose  
dc.subject.classification
Inmunología  
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Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Elevated glucose and oligomeric β-amyloid disrupt synapses via a common pathway of aberrant protein S-nitrosylation  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-03-14T17:04:43Z  
dc.journal.volume
7  
dc.journal.number
1024  
dc.journal.pagination
1-11  
dc.journal.pais
Estados Unidos  
dc.description.fil
Fil: Akhtar, Mohd Waseem. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos  
dc.description.fil
Fil: Sanz Blasco, Sara Isabel. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina  
dc.description.fil
Fil: Dolatabadi, Nima. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos  
dc.description.fil
Fil: Parker, James. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos  
dc.description.fil
Fil: Chon, Kevin. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos  
dc.description.fil
Fil: Lee, Michelle S.. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos  
dc.description.fil
Fil: Soussou, Walid. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos  
dc.description.fil
Fil: McKercher, Scott R.. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos  
dc.description.fil
Fil: Ambasudhan, Rajesh. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos  
dc.description.fil
Fil: Nakamura, Tomohiro. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos  
dc.description.fil
Fil: Lipton, Stuart A.. Sanford Burnham Prebys Medical Discovery Institute. Center for Neuroscience and Aging Research; Estados Unidos. Scintillon Institute. Neurodegenerative Disease Center; Estados Unidos. University of California at San Diego; Estados Unidos  
dc.journal.title
Nature Communications  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/ncomms10242  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729876/  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/ncomms10242