Open Access

Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer's disease

Nambirajan Govindarajan, Pooja Rao, Susanne Burkhardt, Farahnaz Sananbenesi, Oliver M. Schlüter, Frank Bradke, Jianrong Lu, André Fischer

Author Affiliations

  1. Nambirajan Govindarajan1,6,
  2. Pooja Rao1,
  3. Susanne Burkhardt1,2,
  4. Farahnaz Sananbenesi1,2,
  5. Oliver M. Schlüter3,
  6. Frank Bradke4,
  7. Jianrong Lu5 and
  8. André Fischer (afische2{at} *,1,2
  1. 1Department of Psychiatry and Psychotherapy, University Medical Center, Georg‐August‐University Goettingen, Goettingen, Germany
  2. 2German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany
  3. 3Molecular Neurobiology, European Neuroscience Institute Goettingen, Goettingen, Germany
  4. 4German Center for Neurodegenerative Diseases (DZNE) Bonn, Bonn, Germany
  5. 5Department of Biochemistry and Molecular Biology, University of Florida, Gainseville, FL, USA
  6. 6Present address: German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany
  1. *Tel: +49 551 3910378; Fax: +49 551 399836
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Histone deacetylases (HDACs) are currently being discussed as promising therapeutic targets to treat neurodegenerative diseases. However, the role of specific HDACs in cognition and neurodegeneration remains poorly understood. Here, we investigate the function of HDAC6, a class II member of the HDAC superfamily, in the adult mouse brain. We report that mice lacking HDAC6 are cognitively normal but reducing endogenous HDAC6 levels restores learning and memory and α‐tubulin acetylation in a mouse model for Alzheimer's disease (AD). Our data suggest that this therapeutic effect is, at least in part, linked to the observation that loss of HDAC6 renders neurons resistant to amyloid‐β‐mediated impairment of mitochondrial trafficking. Thus, our study suggests that targeting HDAC6 could be a suitable strategy to ameliorate cognitive decline observed in AD.

  • Received August 23, 2012.
  • Revision received October 4, 2012.
  • Accepted October 5, 2012.
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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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