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Role of Histone Deacetylases (HDACs) in Epilepsy and Epileptogenesis

Citraro, R; Leo, A; Constanti, A; Russo, E; (2017) Role of Histone Deacetylases (HDACs) in Epilepsy and Epileptogenesis. Current Pharmaceutical Design , 23 (37) pp. 5546-5562. 10.2174/1381612823666171024130001. Green open access

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Abstract

BACKGROUND: Emerging evidence suggests that epigenetic mechanisms are involved in different brain functions such as the development of the nervous system and normal neuronal function. At the same time, it has been proposed that several neurological diseases are in part, caused by aberrant epigenetic modifications. Nevertheless, the mechanisms underlying pathological alterations in the brain genome are not completely understood. METHODS AND RESULTS: Post-transcriptional histone acetylation is a major mechanism of chromatin remodeling, contributing to epigenetic regulation of gene transcription. Histone deacetylases (HDACs) are a family of proteins involved in both physiological and pathological conditions by regulating the status of chromatin histone acetylation. It is now becoming clear that epigenetic regulatory mechanisms may also play a major role in epilepsy; modulation of chromatin structure through histone modifications has emerged as an important regulator of gene transcription in the brain and altered histone acetylation seems to contribute to changes in gene expression associated with epilepsy and the epileptogenic process. Histone modification is crucial for regulating neurobiological processes such as neural network function, synaptic plasticity, and synaptogenesis which also contribute to the pathophysiology of epilepsy. CONCLUSIONS: The role of epigenetics in epilepsy development is a new and emerging research area; the present article reviews the recent findings on the role played by HDACs and the possible function of different histone modifications in epilepsy and epileptogenesis. Inhibitors of HDACs (HDACIs) have been tested in different experimental models of epilepsy with some success. We also review the results from these studies, which indicate HDACIs as potential new therapeutic agents for the treatment of human epilepsy.

Type: Article
Title: Role of Histone Deacetylases (HDACs) in Epilepsy and Epileptogenesis
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.2174/1381612823666171024130001
Publisher version: https://doi.org/10.2174/1381612823666171024130001
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Epigenetics, chromatin, histone deacetylase (HDAC), histone deacetylase inhibitors (HDACIs), epilepsy, epileptogenesis, brain disorders.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/10030378
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