Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer's disease.
Bottom Line: However, the role of specific HDACs in cognition and neurodegeneration remains poorly understood.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.
Affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany.Show MeSH
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Mentions: Preservation of associative and spatial memory function by reducing Hdac6 is likely to involve multiple cellular processes. To better understand the mechanisms underlying the effect of HDAC6 on memory function in APPPS1-21 mice, we first analysed Aβ plaque load in APPPS1-21 and APPPS1-21-Hdac6−/− mice. Immunohistochemical analysis revealed no difference between the two groups (Fig 4A). Taking into account that disturbances in cytoskeletal integrity play an important role during AD pathogenesis (Stokin et al, 2005), and that one of the best-described roles of HDAC6 is deacetylation of α-tubulin K40ac (Haggarty et al, 2003; Hubbert et al, 2002), we decided to analyze tubulin acetylation in APPPS1-21 and APPPS1-21-Hdac6−/− mice.
Affiliation: Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University Goettingen, Goettingen, Germany.