Epigenetic mechanisms such as histone-acetylation have been implicated with learning and memory and are believed to contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Histone-deacetylase (HDAC) inhibitors were shown to exhibit neuroprotective and neurodegenerative properties in AD animal models, and targeting HDACs appears to be a promising therapeutic strategy for brain diseases. The role of the distinct HDAC proteins in the adult brain is, however, not well understood and so far only pan-HDAC inhibitors have been tested in preclinical settings. Understanding the role of individual HDACs in cognition and AD pathogenesis is therefore vital to develop more selective HDAC inhibitors for the treatment of AD. In this study we investigated the role of HDAC5 in memory function and AD pathogenesis. We show that loss of HDAC5 impairs memory function but has little impact on pathogenesis in a mouse model for amyloid pathology. Our data reveals a novel role of HDAC5 in memory consolidation and shows that future approaches to develop more selective HDAC inhibitors for the treatment of AD should avoid targeting HDAC5.
|Titolo:||Loss of HDAC5 impairs memory function : implications for Alzheimer's disease|
PAVELKA, ZSUZSA (Secondo)
|Parole Chiave:||Alzheimer's disease; amyloid pathology; epigenetics; HDAC inhibitors; histone deacetylases; learning and memory; neurodegenerative diseases|
|Settore Scientifico Disciplinare:||Settore M-FIL/02 - Logica e Filosofia della Scienza|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||10.3233/JAD-2012-121009|
|Appare nelle tipologie:||01 - Articolo su periodico|