Alpha-synuclein deregulates the expression of COL4A2 and impairs ER-Golgi function

in Neurobiology of Disease (2018)

Nuclear localization and phosphorylation modulate pathological effects of Alpha-Synuclein

in Human Molecular Genetics (2018)

HDAC1 links early life stress to schizophrenia-like phenotypes.

in Proceedings of the National Academy of Sciences of the United States of America (2017)

Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression

in Journal of Alzheimer's Disease (2011), 26(1), 187-197

Dysregulation of histone acetylation has been implicated in the onset of age-associated memory impairment and the pathogenesis of neurodegenerative diseases. Elevation of histone acetylation via ... [more ▼]

Dysregulation of histone acetylation has been implicated in the onset of age-associated memory impairment and the pathogenesis of neurodegenerative diseases. Elevation of histone acetylation via administration of histone deacetylase (HDAC) inhibitors is currently being pursued as a novel therapeutic avenue to treat memory impairment linked to Alzheimer's disease (AD). Here we show that severe amyloid pathology correlates with a pronounced dysregulation of histone acetylation in the forebrain of APPPS1-21 mice. Importantly, prolonged treatment with the pan-HDAC inhibitor sodium butyrate improved associative memory in APPPS1-21 mice even when administered at a very advanced stage of pathology. The recovery of memory function correlated with elevated hippocampal histone acetylation and increased expression of genes implicated in associative learning. These data advance our understanding of the potential applicability of HDAC inhibitors for the treatment of AD and suggest that HDAC inhibitors may have beneficial effects even when administered long after the onset of disease-associated symptoms. [less ▲]