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Open Access 01-12-2013 | Review

HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?

Authors: Claudia Simões-Pires, Vincent Zwick, Alessandra Nurisso, Esther Schenker, Pierre-Alain Carrupt, Muriel Cuendet

Published in: Molecular Neurodegeneration | Issue 1/2013

Abstract

Histone deacetylase (HDAC) inhibitors have been demonstrated to be beneficial in animal models of neurodegenerative diseases. Such results were mainly associated with the epigenetic modulation caused by HDACs, especially those from class I, via chromatin deacetylation. However, other mechanisms may contribute to the neuroprotective effect of HDAC inhibitors, since each HDAC may present distinct specific functions within the neurodegenerative cascades. Such an example is HDAC6 for which the role in neurodegeneration has been partially elucidated so far. The strategy to be adopted in promising therapeutics targeting HDAC6 is still controversial. Specific inhibitors exert neuroprotection by increasing the acetylation levels of α-tubulin with subsequent improvement of the axonal transport, which is usually impaired in neurodegenerative disorders. On the other hand, an induction of HDAC6 would theoretically contribute to the degradation of protein aggregates which characterize various neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Hutington’s diseases. This review describes the specific role of HDAC6 compared to the other HDACs in the context of neurodegeneration, by collecting in silico, in vitro and in vivo results regarding the inhibition and/or knockdown of HDAC6 and other HDACs. Moreover, structure, function, subcellular localization, as well as the level of HDAC6 expression within brain regions are reviewed and compared to the other HDAC isoforms. In various neurodegenerative diseases, the mechanisms underlying HDAC6 interaction with other proteins seem to be a promising approach in understanding the modulation of HDAC6 activity.

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Title: HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?
Authors: Claudia Simões-Pires
Vincent Zwick
Alessandra Nurisso
Esther Schenker
Pierre-Alain Carrupt
Muriel Cuendet
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2013
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-8-7

2024 ASCO Annual Meeting

Springer Medicine

HDAC6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?

Abstract

2024 ASCO Annual Meeting

Springer Medicine

Abstract

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