Histone Deacetylase Inhibitors: New Hope for Rheumatoid Arthritis?

Choo, Qiuyi; Ho, Paul C.; Lin, Hai‐Shu

doi:10.2174/138161208784007699

Cited by 52 publications

(43 citation statements)

References 175 publications

(358 reference statements)

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“…[21][22][23][24] Recently evidence has indicated that lignans from Schisandra chinensis have the capacity to suppress the inflammatory response induced by bacterial components such as LPS. 19,25,26) Guo et al (2008) reported that schisandrin inhibited NO production, prostaglandin E 2 release, COX-2, and inducible nitric oxide synthase expression, and that these effects were due to inhibition of NF-B, JNK, and p38 MAPK activities in a Raw 264.7 macrophage cell line. 19) These results are in agreement with ours, because gomisin J, gomisin N, and schisandrin C are also Schisandra chinensis Bail derived lignans, and they inhibited NO production by Raw 264.7 cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Kim

Bae

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Kim

Bae

et al. 2010

Bioscience, Biotechnology, and Biochemistry

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“…86 HDACis suppress proinflammatory cytokine release in cultured PBMCs, macrophages, T cells and epithelial cells [87][88][89][90][91][92][93][94][95] and suppress inflammation in animal models of concanavalin-A-induced hepatitis 92 and lipopolysaccharideinduced endotoxemia. 89,91 HDACis have received significant attention as novel agents for rheumatoid arthritis, 96 capable of reducing inflammation, synovial fibroblast proliferation, joint swelling and bone and cartilage destruction in rodent models of rheumatoid arthritis. [97][98][99][100][101][102] Preclinical efficacy has also been observed in models of inflammatory bowel disease 95,103,104 and central nervous system inflammation.…”

Section: Antiinflammatory Effects Of Hdacismentioning

confidence: 99%

Protein Acetylation in the Cardiorenal Axis

Bush

McKinsey

2010

Circulation Research

114

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Acetylation of histone and nonhistone proteins provides a key mechanism for controlling signaling and gene expression in heart and kidney. Pharmacological inhibition of protein deacetylation with histone deacetylase (HDAC) inhibitors has shown promise in preclinical models of cardiovascular and renal disease. Efficacy of HDAC inhibitors appears to be governed by pleiotropic salutary actions on a variety of cell types and pathophysiological processes, including myocyte hypertrophy, fibrosis, inflammation and epithelial-tomesenchymal transition, and occurs at compound concentrations below the threshold required to elicit toxic side effects. We review the roles of acetylation/deacetylation in the heart and kidney and provide rationale for extending HDAC inhibitors into clinical testing for indications involving these organs. (Circ Res. 2010; 106:272-284.)Key Words: acetylation Ⅲ histone deacetylase Ⅲ heart failure Ⅲ kidney failure Ⅲ fibrosis I t has been estimated that more than 5 million adults in the United States experience heart failure, and more than 20 million adults show signs of chronic kidney disease (CKD). 1,2 Of the patients with heart failure, Ϸ50% experience heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure, which is characterized at the cellular level by myocyte hypertrophy and activation of extracellular matrix (ECM)-producing fibroblasts. Current standard of care for systolic heart failure (eg, ACE inhibitors and ␤-blockers) provide little to no benefit to patients with HFpEF. 3 Likewise, therapy for CKD primarily focuses on lowering blood pressure through modulation of the renin-angiotensin system and maintaining blood glucose control, and this strategy only minimally slows the glomerular injury and insidious fibrotic mechanisms that culminate in end-stage renal disease. 4 The high rate of morbidity and mortality in patients with HFpEF and CKD underscores the urgent need for novel therapeutics. Histone deacetylases (HDACs) are emerging as key players in the pathogenesis of these diseases, suggesting unexpected potential for pharmacological inhibitors of HDACs in the treatment of disorders of the cardiorenal axis.Histone acetyltransferases (HATs) and HDACs act in an opposing manner to control the acetylation state of proteins. The most well characterized role for protein acetylation is in Original received September 15, 2009; revision received October 6, 2009; accepted October 27, 2009 the control of gene transcription. Acetylation of the -amino groups of lysine residues in nucleosomal histone tails by HATs is thought to relax chromatin structure by weakening the interaction of the positively charged histone tails with the negatively charged phosphate backbone of DNA, allowing access of transcriptional activators and gene induction. Deacetylation of histones by HDACs alters the electrostatic properties of chromatin in a manner that favors gene repression. Interestingly, a recent genome-wide chromatin immunoprecipitation analysis revealed preferen...

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“…Modulation of these enzymes using HDAC inhibitors (HDACi) is emerging as a promising treatment not only for cancer [1][2][3] but also for neurodegenerative diseases, asthma, rheumatoid arthritis, viral infections and malaria [4][5][6][7][8][9][10][11]. A number of HDACi have progressed to the clinic, or are in clinical trials, for treating solid and haematological tumours [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylases (HDAC) in physiological and pathological bone remodelling

Cantley

Zannettino

Bartold

et al. 2017

Bone

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Histone deacetylases (HDACs) 1 play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi) 2 that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are currently being studied also for their efficacy in nonmalignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes.Selective isozyme-specific inhibitors currently being developed against class I HDAC (1, 2, 3 and 8) and class II HDAC (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease.

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Histone Deacetylase Inhibitors: New Hope for Rheumatoid Arthritis?

Cited by 52 publications

References 175 publications

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Anti-Inflammatory Effects of Gomisin N, Gomisin J, and Schisandrin C Isolated from the Fruit ofSchisandra chinensis

Protein Acetylation in the Cardiorenal Axis

Histone deacetylases (HDAC) in physiological and pathological bone remodelling

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