A combination drug therapy improves cognition and reverses gene expression changes in a mouse model of Huntington's disease

Background: Histone deacetylases (HDAC) are an important class of enzymes that play a pivotal role in epigenetic regulation of gene expression that modifies the terminal of core histones leading to remodelling of chromatin topology and thereby controlling gene expression. HDAC inhibitors (HDACi) counter this action and can result in hyperacetylation of histones, thereby inducing an array of cellular consequences such as activation of apoptotic pathways, generation of reactive oxygen species (ROS), cell cycle arrest and autophagy. Hence, there is a growing interest in the potential clinical use of HDAC inhibitors as a new class of targeted cancer therapeutics. Methodology and Result: Several research articles spanning between 2016 and 2017 were reviewed in this article and presently offer critical insights into the important strategies such as structure-based rational drug design, multi-parameter lead optimization methodologies, relevant SAR studies and biology of various class of HDAC inhibitors, such as hydroxamic acids, benzamides, cyclic peptides, aliphatic acids, summarising the clinical trials and results of various combination drug therapy till date. Conclusion: This review will provide a platform to the synthetic chemists and biologists to cater the needs of both molecular targeted therapy and combination drug therapy to design and synthesize safe and selective HDAC inhibitors in cancer therapeutics.

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Longitudinal analysis of gene expression and behaviour in the HdhQ150 mouse model of Huntington's disease

Brain Research Bulletin ◽

10.1016/j.brainresbull.2011.10.001 ◽

2012 ◽

Vol 88 (2-3) ◽

pp. 199-209 ◽

Cited By ~ 16

Author(s):

Peter Giles ◽

Lyn Elliston ◽

Gemma V. Higgs ◽

Simon P. Brooks ◽

Stephen B. Dunnett ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Longitudinal Analysis

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Brain gene expression correlates with changes in behavior in the R6/1 mouse model of Huntington’s disease

Genes Brain & Behavior ◽

10.1111/j.1601-183x.2007.00350.x ◽

2008 ◽

Vol 7 (3) ◽

pp. 288-299 ◽

Cited By ~ 36

Author(s):

A. Hodges ◽

G. Hughes ◽

S. Brooks ◽

L. Elliston ◽

P. Holmans ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Brain Gene Expression

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Nicotinamide improves motor deficits and upregulates PGC-1α and BDNF gene expression in a mouse model of Huntington's disease

Neurobiology of Disease ◽

10.1016/j.nbd.2010.08.017 ◽

2011 ◽

Vol 41 (1) ◽

pp. 43-50 ◽

Cited By ~ 72

Author(s):

Tyisha Hathorn ◽

Abigail Snyder-Keller ◽

Anne Messer

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Motor Deficits ◽

Bdnf Gene

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Pharmacological Imposition of Sleep Slows Cognitive Decline and Reverses Dysregulation of Circadian Gene Expression in a Transgenic Mouse Model of Huntington's Disease

Journal of Neuroscience ◽

10.1523/jneurosci.0649-07.2007 ◽

2007 ◽

Vol 27 (29) ◽

pp. 7869-7878 ◽

Cited By ~ 118

Author(s):

P. N. Pallier ◽

E. S. Maywood ◽

Z. Zheng ◽

J. E. Chesham ◽

A. N. Inyushkin ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Cognitive Decline ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Circadian Gene

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Drug Therapy of Experimental Tuberculosis (TB): Improved Outcome by Combining SQ109, a New Diamine Antibiotic, with Existing TB Drugs

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01326-06 ◽

2007 ◽

Vol 51 (4) ◽

pp. 1563-1565 ◽

Cited By ~ 95

Author(s):

Boris V. Nikonenko ◽

Marina Protopopova ◽

Rowena Samala ◽

Leo Einck ◽

Carol A. Nacy

Keyword(s):

Drug Therapy ◽

Mouse Model ◽

Combination Drug Therapy ◽

First Line ◽

Combination Drug ◽

Experimental Tuberculosis ◽

Improved Outcome

ABSTRACT Substitution of the new diamine antibiotic SQ109 for ethambutol in a mouse model of chronic tuberculosis (TB) improved efficacy of combination drug therapy with first-line TB drugs rifampin and isoniazid, with or without pyrazinamide: at 8 weeks, lung bacteria were 1.5 log10 lower in SQ109-containing regimens.

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