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Role of Histone Deacetylases (HDACs) in Epilepsy and Epileptogenesis

[ Vol. 23 , Issue. 37 ]

Author(s):

Rita Citraro, Antonio Leo, Matteo Santoro, Giuseppe D`agostino, Andrew Constanti and Emilio Russo*   Pages 5546 - 5562 ( 17 )

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.

Keywords:

Epigenetics, chromatin, histone deacetylase (HDAC), histone deacetylase inhibitors (HDACIs), epilepsy, epileptogenesis, brain disorders.

Affiliation:

Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro, Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro, School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD Scotland, The Rowett Institute, University of Aberdeen Foresterhill, Aberdeen, AB25 2ZD Scotland, Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London, Department of Science of Health, School of Medicine and Surgery, University of Catanzaro, Catanzaro



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