Epigenetic approaches for bipolar disorder drug discovery

Peedicayil, Jacob

doi:10.1517/17460441.2014.922537

Cited by 15 publications

(8 citation statements)

References 104 publications

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“…Therapeutic interventions by epigenetic modifications range from the discovery of the epigenetic mechanism of well-implemented mood stabilizers to substances that are currently being developed or that show promising results in preclinical trials. 106 Exciting developments are occurring around EpiEffectors, engineered transcription factors such as transcription activator-like effectors or zinc-finger-proteins, which have been designed to bind at specific loci in the genome. These newly introduced chromatin changes have only been tested in animal models so far, but show promising results in the field of neuroscience.…”

Section: Psychosis In Bd As a Shared Traitmentioning

confidence: 99%

Dissecting bipolar disorder complexity through epigenomic approach

Ludwig

Dwivedi

2016

Mol Psychiatry

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In recent years, numerous studies of gene regulation mechanisms have emerged in neuroscience. Epigenetic modifications, described as heritable but reversible changes, include DNA methylation, DNA hydroxymethylation, histone modifications and noncoding RNAs. The pathogenesis of psychiatric disorders, such as bipolar disorder, may be ascribed to a complex gene–environment interaction (G × E) model, linking the genome, environmental factors and epigenetic marks. Both the high complexity and the high heritability of bipolar disorder make it a compelling candidate for neurobiological analyses beyond DNA sequencing. Questions that are being raised in this review are the precise phenotype of the disorder in question, and also the trait versus state debate and how these concepts are being implemented in a variety of study designs.

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Section: Psychosis In Bd As a Shared Traitmentioning

confidence: 99%

Dissecting bipolar disorder complexity through epigenomic approach

Ludwig

Dwivedi

2016

Mol Psychiatry

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“…Several studies have demonstrated that the HDAC inhibitors, VPA and SB, present an antidepressant and antimanic effect in pre‐clinical studies (Resende et al., 2013). Together, these favourable results suggest that HDAC modulation may have an important role in behavioural management of mood disorders; however, the mechanisms underlying this effects and the interaction of these drugs with other epigenetic markers in this disorder are not completely clear (Peedicayil, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have to focus on new agents with possible therapeutic effects in BD. Among these targets, it highlights the epigenetics modulators, such as VPA (Peedicayil, 2014). One of the VPA mechanisms of action is the inhibition of HDAC activity, which has been a target extensively studied for BD treatment (Konstantakopoulos, Dimitrakopoulos, & Michalopoulou, 2015).…”

Section: Introductionmentioning

confidence: 99%

Role of epigenetic regulatory enzymes in animal models of mania induced by amphetamine and paradoxical sleep deprivation

Varela

Resende²,

Dal‐Pont³

et al. 2020

Eur J of Neuroscience

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It is known that bipolar disorder has a multifactorial aetiology where the interaction between genetic and environmental factors is responsible for its development. Because of this, epigenetics has been largely studied in psychiatric disorders. The present study aims to evaluate the effects of histone deacetylase inhibitors on epigenetic enzyme alterations in rats or mice submitted to animal models of mania induced by dextro‐amphetamine or sleep deprivation, respectively. Adult male Wistar rats were subjected to 14 days of dextro‐amphetamine administration, and from the eighth to the fourteenth day, the animals were treated with valproate and sodium butyrate in addition to dextro‐amphetamine injections. Adult C57BL/6 mice received 7 days of valproate or sodium butyrate administration, being sleep deprived at the last 36 hr of the protocol. Locomotor and exploratory activities of rats and mice were evaluated in the open‐field test, and histone deacetylase, DNA methyltransferase, and histone acetyltransferase activities were assessed in the frontal cortex, hippocampus, and striatum. Dextro‐amphetamine and sleep deprivation induced hyperactivity and increased histone deacetylase and DNA methyltransferase activities in the animal's brain. Valproate and sodium butyrate were able to reverse hyperlocomotion induced by both animal models, as well as the alterations on histone deacetylase and DNA methyltransferase activities. There was a positive correlation between enzyme activities and number of crossings for both models. Histone deacetylase and DNA methyltransferase activities also presented a positive correlation between theirselves. These results suggest that epigenetics can play an important role in BD pathophysiology as well as in its treatment.

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“…The purpose of this work is to review the recent literature on the use of HDACi in cancer therapies. Epigenetics is a way of regulating gene expression without directly interfering DNA sequence and involves mechanisms such as histone and non-histone modifications, chromatin remodeling, DNA methylation or RNA regulations [4]. Histone deacetylase (HDAC) enzymes are particularly important since their interaction with lysine residues plays crucial role in chromatin remodeling by ensuring balance in gene expression.…”

Section: Introduction and Purposementioning

confidence: 99%

The efficacy of HDAC inhibitors in neoplasm treatment

Psiuk

Rocka

Żak

et al. 2020

J Educ Health Sport

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Introduction and purpose: Histone Deacetylases (HDACs) are associated with epigenetic regulation of gene expression. They are responsible of adequate action of not only histone proteins, but also crucial cell cycle proteins, such as p53, NF-κB or alpha tubulin. Recent studies have shown the connection between expression of HDAC and carcinogenesis and impact of HDAC inhibitors on cancer therapy. The aim of the study was to review the recent studies on HDAC inhibitors efficiency in the treatment of hematologic neoplasms and solid tumors. It is a study review from 2010 to 2020 using the PubMed database and ClinicalTrials.gov. Description of state of knowledge: Most studies related to HDAC inhibitors impact in hematological neoplasms, such as multiple myeloma, Hodgkin lymphoma, T-cell lymphomas and acute myeloid leukemia. Among studied agents panobinostat, vorinostat and showed efficacy. Moreover, some HDACi demonstrated effectiveness in solid tumors treatment, foremost vorinostat in breast cancer and entinostat in non-small cell lung lymphoma. Summary: Including HDAC inhibitors in tumor treatment could be beneficial for patients, especially those with advanced, relapsed or refractory hematologic neoplasm. However, further studies are necessary to confirm their efficacy and to reveal side effects.

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Epigenetic approaches for bipolar disorder drug discovery

Cited by 15 publications

References 104 publications

Dissecting bipolar disorder complexity through epigenomic approach

Dissecting bipolar disorder complexity through epigenomic approach

Role of epigenetic regulatory enzymes in animal models of mania induced by amphetamine and paradoxical sleep deprivation

The efficacy of HDAC inhibitors in neoplasm treatment

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