title: Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer's disease.
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.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany.
authors.forename: Nambirajan
authors.initials: N
authors.lastname: Govindarajan
authors.forename: Pooja
authors.initials: P
authors.lastname: Rao
authors.forename: Susanne
authors.initials: S
authors.lastname: Burkhardt
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sananbenesi
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.forename: Frank
authors.initials: F
authors.lastname: Bradke
authors.forename: Jianrong
authors.initials: J
authors.lastname: Lu
authors.forename: André
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000107:Acetylation; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000523:psychology* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D014404:Tubulin; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases