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http://purl.uniprot.org/citations/22236576http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22236576http://www.w3.org/2000/01/rdf-schema#comment"

Background/aims

Long-term memory requires fine-tuning regulation of gene expression in specific neural circuits of the brain. Transcriptional regulation of gene programs is a key mechanism for memory storage and its deregulation may contribute to synaptic and cognitive dysfunction in memory disorders. The molecular mechanisms underlying changes on activity-dependent gene expression in Alzheimer's disease (AD) are largely unknown.

Methods

We analyzed the expression of activity-dependent genes regulated by the cAMP response element binding protein (CREB) and activation of CREB and its coactivator CREB-regulated transcription coactivator 1 (CRTC1) in control and mutant β-amyloid precursor protein (APP(Sw,Ind); Swedish and Indiana mutations) transgenic mice.

Results

Gene expression analyses revealed specific downregulation of a subset of well-known activity-induced CREB-dependent genes, including c-fos, Bdnf and Nr4a2, in the hippocampus of memory-impaired APP(Sw,Ind) transgenic mice. Activity-dependent CREB transcription induced by calcium/cAMP signals is disrupted through a mechanism involving deregulation of calcium/calcineurin-mediated dephosphorylation and activation of CRTC1. Expression of CRTC1 and pharmacological activation of L-type voltage-gated calcium channels reverse the deficits in CRTC1-mediated transcription in APP(Sw,Ind) neurons.

Conclusion

Our results suggest that CRTC1 dysfunction caused by Aβ accumulation underlies changes in gene expression required for hippocampal-dependent memory in AD transgenic mice."xsd:string
http://purl.uniprot.org/citations/22236576http://purl.org/dc/terms/identifier"doi:10.1159/000333341"xsd:string
http://purl.uniprot.org/citations/22236576http://purl.uniprot.org/core/author"Saura C.A."xsd:string
http://purl.uniprot.org/citations/22236576http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22236576http://purl.uniprot.org/core/name"Neurodegener Dis"xsd:string
http://purl.uniprot.org/citations/22236576http://purl.uniprot.org/core/pages"250-252"xsd:string
http://purl.uniprot.org/citations/22236576http://purl.uniprot.org/core/title"CREB-regulated transcription coactivator 1-dependent transcription in Alzheimer's disease mice."xsd:string
http://purl.uniprot.org/citations/22236576http://purl.uniprot.org/core/volume"10"xsd:string
http://purl.uniprot.org/citations/22236576http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22236576
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http://purl.uniprot.org/uniprot/#_Q6UUV9-mappedCitation-22236576http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22236576
http://purl.uniprot.org/uniprot/#_Q8IZL2-mappedCitation-22236576http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22236576
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