1. Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer's disease
- Author
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Susanne Burkhardt, Nambirajan Govindarajan, Farahnaz Sananbenesi, Oliver M. Schlüter, Jianrong Lu, Andre Fischer, Pooja Rao, and Frank Bradke
- Subjects
Male ,cognition ,psychology [Alzheimer Disease] ,genetics [Alzheimer Disease] ,Disease ,Histone Deacetylase 6 ,genetics [Histone Deacetylases] ,Mice ,0302 clinical medicine ,Tubulin ,Cognitive decline ,Research Articles ,Genetics ,Mice, Knockout ,Neurons ,0303 health sciences ,biology ,Neurodegeneration ,physiology [Cognition] ,neurodegeneration ,Brain ,Cognition ,Acetylation ,metabolism [Tubulin] ,Alzheimer's disease ,Histone ,metabolism [Neurons] ,Molecular Medicine ,physiology [Histone Deacetylases] ,epigenetics ,histone deacetylase ,metabolism [Amyloid beta-Peptides] ,Histone Deacetylases ,03 medical and health sciences ,Alzheimer Disease ,Memory ,medicine ,Animals ,Humans ,Learning ,ddc:610 ,physiology [Learning] ,Epigenetics ,physiology [Memory] ,030304 developmental biology ,Amyloid beta-Peptides ,therapy [Alzheimer Disease] ,enzymology [Alzheimer Disease] ,HDAC6 ,medicine.disease ,deficiency [Histone Deacetylases] ,Hdac6 protein, mouse ,Disease Models, Animal ,metabolism [Brain] ,biology.protein ,Histone deacetylase ,Neuroscience ,030217 neurology & neurosurgery - 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. peerReviewed
- Published
- 2012
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