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

Authors

  • Nambirajan Govindarajan,

    1. Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany
    2. Present address: German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany
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  • Pooja Rao,

    1. Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany
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  • Susanne Burkhardt,

    1. Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany
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  • Farahnaz Sananbenesi,

    1. Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany
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  • Oliver M. Schlüter,

    1. Molecular Neurobiology, European Neuroscience Institute Goettingen, Goettingen, Germany
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  • Frank Bradke,

    1. German Center for Neurodegenerative Diseases (DZNE) Bonn, Bonn, Germany
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  • Jianrong Lu,

    1. Department of Biochemistry and Molecular Biology, University of Florida, Gainseville, FL, USA
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  • André Fischer

    Corresponding author
    1. Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany
    2. German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany
    • Tel: +49 551 3910378; Fax: +49 551 399836

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Abstract

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.

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