Histone deacetylases as targets in autoimmune and autoinflammatory diseases

Hamminger, Patricia; Rica, Ramona; Ellmeier, Wilfried

doi:10.1016/bs.ai.2020.06.001

Cited by 24 publications

(16 citation statements)

References 240 publications

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“…Treatment with the dual SYK/JAK inhibitor cerdulatinib showed induction of apoptosis in CLL cells and reduced capacity to produce CCL3 and CCL4 [ 155 , 156 ], two chemokines that are induced upon interaction with nurse-like cells, which are supporting tumor-associated macrophages in CLL. It is also attractive to explore combination therapies of BTK inhibitors with histone deacetylase inhibitors (HDACis), as they have demonstrated potential in autoimmune animal models, and use of isoform selective HDACis may overcome adverse effects [ 157 ]. Combination therapy with ibrutinib and HDACis affected the survival of CLL cells in the EμTCL -1 CLL mouse model and induced synergistic cytotoxicity in primary cells from CLL patients [ 158 ].…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Bruton’s Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease

Neys

Rip

Hendriks

et al. 2021

Drugs

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Systemic autoimmune disorders are complex heterogeneous chronic diseases involving many different immune cells. A significant proportion of patients respond poorly to therapy. In addition, the high burden of adverse effects caused by “classical” anti-rheumatic or immune modulatory drugs provides a need to develop more specific therapies that are better tolerated. Bruton’s tyrosine kinase (BTK) is a crucial signaling protein that directly links B-cell receptor (BCR) signals to B-cell activation, proliferation, and survival. BTK is not only expressed in B cells but also in myeloid cells, and is involved in many different signaling pathways that drive autoimmunity. This makes BTK an interesting therapeutic target in the treatment of autoimmune diseases. The past decade has seen the emergence of first-line BTK small-molecule inhibitors with great efficacy in the treatment of B-cell malignancies, but with unfavorable safety profiles for use in autoimmunity due to off-target effects. The development of second-generation BTK inhibitors with superior BTK specificity has facilitated the investigation of their efficacy in clinical trials with autoimmune patients. In this review, we discuss the role of BTK in key signaling pathways involved in autoimmunity and provide an overview of the different inhibitors that are currently being investigated in clinical trials of systemic autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus, as well as available results from completed trials.

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Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Bruton’s Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease

Neys

Rip

Hendriks

et al. 2021

Drugs

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“…Histone modifications, such as acetylation, methylation, and phosphorylation, represent one of the key epigenetic processes that exert a global control of gene expression. 40 Histone acetyltransferases (HAT) and HDACs play essential roles in these processes. For example, butyrate, a Class I HDAC inhibitor, can significantly alter the transcriptome in vitro.…”

Section: Discussionmentioning

confidence: 99%

Ellagitannin Punicalagin Disrupts the Pathways Related to Bacterial Growth and Affects Multiple Pattern Recognition Receptor Signaling by Acting as a Selective Histone Deacetylase Inhibitor

Liu

Smith

Wang

et al. 2023

J. Agric. Food Chem.

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Punicalagin (PA) is a key ellagitannin abundant in pomegranate with wide-ranging biological activities. In this study, we examined the biological processes by which PA regulates bacterial growth and inflammation in human cells using multiomics and molecular docking approaches. PA promoted macrophage-mediated bacterial killing and inhibited the growth of Citrobacter rodentium by inducing a distinct metabolome pattern. PA acted as a selective regulator of histone deacetylases (HDACs) and affected 37 pathways in macrophages, including signaling mediated by pattern recognition receptors, such as Toll-like and NOD-like receptors. In silico simulation showed that PA can bind with high affinity to HDAC7. PA downregulated HDAC7 at both mRNA and protein levels and resulted in a decrease in the level of histone 3 lysine 27 acetylation. Our findings provide evidence that PA exerts its biological effects via multiple pathways, which can be exploited in the development of this bioactive food ingredient for disease management.

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“…They have also been investigated as a potential therapeutic avenue to treat diabetes as HDACs contribute to glucose homeostasis in mammals [ 116 , 117 , 118 , 119 , 120 ]. Immune-mediated diseases such as chronic obstructive pulmonary disease, rheumatoid arthritis, and inflammatory bowel disease are further examples of diseases where HDACi treatment is being investigated [ 121 , 122 ].…”

Section: Hdacs Therapies: Approved Trials and Future Directionsmentioning

confidence: 99%

Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets

Gomez-Sanchez

Patel

Martirena

et al. 2022

IJMS

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The peripheral nervous system (PNS) has a remarkable regenerative capacity in comparison to the central nervous system (CNS), a phenomenon that is impaired during ageing. The ability of PNS axons to regenerate after injury is due to Schwann cells (SC) being reprogrammed into a repair phenotype called Repair Schwann cells. These repair SCs are crucial for supporting axonal growth after injury, myelin degradation in a process known as myelinophagy, neurotropic factor secretion, and axonal growth guidance through the formation of Büngner bands. After regeneration, repair SCs can remyelinate newly regenerated axons and support nonmyelinated axons. Increasing evidence points to an epigenetic component in the regulation of repair SC gene expression changes, which is necessary for SC reprogramming and regeneration. One of these epigenetic regulations is histone acetylation by histone acetyl transferases (HATs) or histone deacetylation by histone deacetylases (HDACs). In this review, we have focused particularly on three HDAC classes (I, II, and IV) that are Zn2+-dependent deacetylases. These HDACs are important in repair SC biology and remyelination after PNS injury. Another key aspect explored in this review is HDAC genetic compensation in SCs and novel HDAC inhibitors that are being studied to improve nerve regeneration.

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Histone deacetylases as targets in autoimmune and autoinflammatory diseases

Cited by 24 publications

References 240 publications

Bruton’s Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease

Bruton’s Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease

Ellagitannin Punicalagin Disrupts the Pathways Related to Bacterial Growth and Affects Multiple Pattern Recognition Receptor Signaling by Acting as a Selective Histone Deacetylase Inhibitor

Emerging Role of HDACs in Regeneration and Ageing in the Peripheral Nervous System: Repair Schwann Cells as Pivotal Targets

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