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microRNA‐34c is a novel target to treat dementias

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TLDR
The data suggest that miR‐34c could be a marker for the onset of cognitive disturbances linked to AD and indicate that targeting miR-34ccould be a suitable therapy.
Abstract
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.

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Journal ArticleDOI

The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila

TL;DR: It is reported that the conserved miRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration.
Journal ArticleDOI

MicroRNAs in neuronal function and dysfunction.

TL;DR: Evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction is reviewed.
Journal ArticleDOI

Adult-specific functions of animal microRNAs

TL;DR: This Review examines evidence that miRNAs have continuous roles in adults in ways that are separable from developmental control and discusses methods for studying miRNA activities specifically in adults and evaluate their relative strengths and weaknesses.
Journal ArticleDOI

The epigenetics of aging and neurodegeneration.

TL;DR: Current knowledge about the major epigenetic mechanisms, including DNA methylation and DNA demethylation, chromatin remodeling and non-coding RNAs, as well as the involvement of these mechanisms in normal aging and in the pathophysiology of the most common neurodegenerative diseases are reviewed.
References
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Journal ArticleDOI

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TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
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Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets

TL;DR: In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of the gene set.
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MicroRNAs: small RNAs with a big role in gene regulation

TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
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Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?

TL;DR: This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of micro RNA function.
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Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide.

TL;DR: Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins.
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