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Pharmaceuticals
Special Issues
HDAC Inhibitors 2014
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HDAC Inhibitors 2014

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (15 October 2014) | Viewed by 25886

Special Issue Editor

Prof. Dr. David T. Dexter

E-Mail Website
Guest Editor
Parkinson’s Disease Research Group, Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, London, UK
Interests: mechanisms of cell death; neuroprotection in Parkinson's disease

Special Issue Information

Dear Colleagues,

The journal “Pharmaceuticals” is planning to publish a special issue covering the topic “HDAC Inhibitors” and I am cordially inviting you to contribute an article to this volume.

Histone deacetylases (HDACs) are a group of enzymes capable of catalyzing the hydrolysis of N-acetyl lysine residues of histones which package chromosomal DNA. This causes the condensation or more tightly coiling of DNA around the histones leading the repression of DNA transcription. Therefore HDACs play an important role in mediating gene expression and cell proliferation. To date, 18 human HDAC isoforms have been characterised:  based on their sequence homologies and co-factor dependencies they have been phylogenetically categorised into 4 main classes: class I, II (a and b), III and IV. HDAC inhibitors (HDACIs) have not only shown promise as antiparasitic, antineurodegenerative, antirheumatologic agents and immunosuppressant, but also as potent anticancer agents. This special issue invites original research articles, including review articles, on the pharmacology, biological effects, mechanisms of action and the clinical development of HDACIs for a variety of diseases.

Prof. Dr. David T Dexter
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • histone deacetylase inhibitors (HDACIs)
  • epigenetic modifications
  • DNA transcription
  • histones
  • neurodegeneration
  • anti-inflammatory/immune modulation, anticancer

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Published Papers (2 papers)

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Research

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2854 KiB  
Article
Involvement of the Antioxidant Effect and Anti-inflammatory Response in Butyrate-Inhibited Vascular Smooth Muscle Cell Proliferation
by Omana P. Mathew, Kasturi Ranganna and Shirlette G. Milton
Pharmaceuticals 2014, 7(11), 1008-1027; https://doi.org/10.3390/ph7111008 - 10 Nov 2014
Cited by 41 | Viewed by 10326
Abstract
Epigenetic mechanisms by altering the expression and, in turn, functions of target genes have potential to modify cellular processes that are characteristics of atherosclerosis, including inflammation, proliferation, migration and apoptosis/cell death. Butyrate, a natural epigenetic modifier and a histone deacetylase inhibitor (HDACi), is [...] Read more.
Epigenetic mechanisms by altering the expression and, in turn, functions of target genes have potential to modify cellular processes that are characteristics of atherosclerosis, including inflammation, proliferation, migration and apoptosis/cell death. Butyrate, a natural epigenetic modifier and a histone deacetylase inhibitor (HDACi), is an inhibitor of vascular smooth muscle cell (VSMC) proliferation, a critical event in atherogenesis. Here, we examined whether glutathione peroxidases (GPxs), a family of antioxidant enzymes, are modulated by butyrate, contributing to its antiproliferation action on VSMC through the regulation of the inflammatory response by using western blotting, immunostaining methods and activity assay. Treatment of VSMC with butyrate not only upregulates glutathione peroxidase (GPx) 3 and GPx4, but also increases the overall catalytic activity of GPx supporting involvement of antioxidant effect in butyrate arrested VSMC proliferation. Moreover, analysis of the redox-sensitive NF-κB transcription factor system, the target of GPx, reveals that butyrate causes downregulation of IKKα, IKKβ, IkBα and NF-κBp65 expression and prevents NF-κBp65 phosphorylation at serine536 causing inhibition of the expression NF-κB target inflammatory genes, including inducible nitric oxide synthase, VCAM-1 and cyclooxygenase-2. Overall, these observations suggest a link between the antioxidant effect and anti-inflammatory response in butyrate-arrested VSMC proliferation, accentuating the atheroprotective and therapeutic potential of natural products, like butyrate, in vascular proliferative diseases. Full article
(This article belongs to the Special Issue HDAC Inhibitors 2014)
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Review

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Review
Involvement of HDAC1 and HDAC3 in the Pathology of Polyglutamine Disorders: Therapeutic Implications for Selective HDAC1/HDAC3 Inhibitors
by Elizabeth A. Thomas
Pharmaceuticals 2014, 7(6), 634-661; https://doi.org/10.3390/ph7060634 - 26 May 2014
Cited by 37 | Viewed by 14946
Abstract
Histone deacetylases (HDACs) enzymes, which affect the acetylation status of histones and other important cellular proteins, have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Emerging studies have demonstrated that different types of HDAC inhibitors show beneficial [...] Read more.
Histone deacetylases (HDACs) enzymes, which affect the acetylation status of histones and other important cellular proteins, have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Emerging studies have demonstrated that different types of HDAC inhibitors show beneficial effects in various experimental models of neurological disorders. HDAC enzymes comprise a large family of proteins, with18 HDAC enzymes currently identified in humans. Hence, an important question for HDAC inhibitor therapeutics is which HDAC enzyme(s) is/are important for the amelioration of disease phenotypes, as it has become clear that individual HDAC enzymes play different biological roles in the brain. This review will discuss evidence supporting the involvement of HDAC1 and HDAC3 in polyglutamine disorders, including Huntington’s disease, and the use of HDAC1- and HDAC3-selective HDAC inhibitors as therapeutic intervention for these disorders. Further, while HDAC inhibitors are known alter chromatin structure resulting in changes in gene transcription, understanding the exact mechanisms responsible for the preclinical efficacy of these compounds remains a challenge. The potential chromatin-related and non-chromatin-related mechanisms of action of selective HDAC inhibitors will also be discussed. Full article
(This article belongs to the Special Issue HDAC Inhibitors 2014)
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