microRNA-34c is a novel target to treat dementias

MicroRNAs are key regulators of transcriptome plasticity and have been implicated with the pathogenesis of brain diseases. Here, we employed massive parallel sequencing and provide, at an unprecedented depth, the complete and quantitative miRNAome of the mouse hippocampus, the prime target of neurod...

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Bibliographic Details
Published in:The EMBO journal 2011-10, Vol.30 (20), p.4299-4308
Main Authors: Zovoilis, Athanasios, Agbemenyah, Hope Y, Agis-Balboa, Roberto C, Stilling, Roman M, Edbauer, Dieter, Rao, Pooja, Farinelli, Laurent, Delalle, Ivana, Schmitt, Andrea, Falkai, Peter, Bahari-Javan, Sanaz, Burkhardt, Susanne, Sananbenesi, Farahnaz, Fischer, Andre
Format: Article
Language:English
Subjects:
Aged
Alzheimer Disease - metabolism
Alzheimer's disease
Animals
cognitive diseases
Dementia
EMBO24
EMBO27
Female
gene expression
Genetics
hippocampus
Hippocampus - metabolism
Humans
learning & memory
Male
Memory Disorders - metabolism
Mice
Mice, Inbred C57BL
MicroRNAs - metabolism
miRNA
Pathogenesis
Plasticity
Ribonucleic acid
RNA
Transcriptome
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Summary:MicroRNAs are key regulators of transcriptome plasticity and have been implicated with the pathogenesis of brain diseases. Here, we employed massive parallel sequencing and provide, at an unprecedented depth, the complete and quantitative miRNAome of the mouse hippocampus, the prime target of neurodegenerative diseases such as Alzheimer's disease (AD). Using integrative genetics, we identify miR‐34c as a negative constraint of memory consolidation and show that miR‐34c levels are elevated in the hippocampus of AD patients and corresponding mouse models. In line with this, targeting miR‐34 seed rescues learning ability in these mouse models. Our data suggest that miR‐34c could be a marker for the onset of cognitive disturbances linked to AD and indicate that targeting miR‐34c could be a suitable therapy. The miRNAome of the mouse hippocampus reveals miR‐34c as a specific negative regulator of memory formation. miR‐34c levels are elevated in a mouse model of Alzheimer's Disease as well as in Alzheimer's patients, and miR‐34c inhibition restores memory performance in the animal model.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2011.327