期刊
EMBO JOURNAL
卷 30, 期 20, 页码 4299-4308出版社
WILEY
DOI: 10.1038/emboj.2011.327
关键词
cognitive diseases; gene expression; hippocampus; learning & memory; miRNA
资金
- EURYI
- ERA-Net Neuron Project Epitherapy
- Hans and Ilse Breuer Foundation
- Schram-Foundation
- German Research Foundation [SA/1050/2-1]
- EMBO
- DZNE
- German Center for Neurodegenerative Diseases Munich
- Max Planck Society
- University Medical Center of the Georg August University Gottingen
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 EMBO Journal (2011) 30, 4299-4308. doi: 10.1038/emboj.2011.327; Published online 23 September 2011
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