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microRNA‐34c is a novel target to treat dementias

Athanasios Zovoilis, Hope Y Agbemenyah, Roberto C Agis‐Balboa, Roman M Stilling, Dieter Edbauer, Pooja Rao, Laurent Farinelli, Ivana Delalle, Andrea Schmitt, Peter Falkai, Sanaz Bahari‐Javan, Susanne Burkhardt, Farahnaz Sananbenesi, Andre Fischer

Author Affiliations

  1. Athanasios Zovoilis1,,
  2. Hope Y Agbemenyah1,,
  3. Roberto C Agis‐Balboa1,
  4. Roman M Stilling1,
  5. Dieter Edbauer2,
  6. Pooja Rao1,
  7. Laurent Farinelli3,
  8. Ivana Delalle4,
  9. Andrea Schmitt5,6,
  10. Peter Falkai6,7,
  11. Sanaz Bahari‐Javan1,
  12. Susanne Burkhardt1,
  13. Farahnaz Sananbenesi1 and
  14. Andre Fischer*,1,6,7
  1. 1 Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Göttingen, Germany
  2. 2 DZNE, German Center for Neurodegenerative Diseases Munich, Munich, Germany
  3. 3 Fasteris SA, Geneva, Switzerland
  4. 4 Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA
  5. 5 Laboratory of Neuroscience (LIM27), Institute of Psychiatry, University of Sao Paulo, São Paulo, Brazil
  6. 6 Department of Psychiatry and Psychotherapy, University of Göttingen, von‐Göttingen, Germany
  7. 7 DZNE, German Center for Neurodegenerative Diseases Göttingen, Göttingen, Germany
  1. *Corresponding author. Department for Psychiatry and Psychotherapy, European Neuroscience Institute, Grisebach Strasse 3, Göttingen 37077, Germany. Tel.: +49 551 391 0378; Fax: +49 551 399 836; E-mail: afische2{at}gwdg.de
  1. These authors contributed equally to this work

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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.

There is a Have you seen? (October 2011) associated with this Article.

  • Received March 17, 2011.
  • Accepted August 9, 2011.
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