Abstract
Around three million patients die due to airway inflammatory diseases each year. The most notable of these diseases are asthma and chronic obstructive pulmonary disease (COPD). Therefore, new therapies are urgently needed. Promising targets are histone deacetylases (HDACs), since they regulate posttranslational protein acetylation. Over a thousand proteins are reversibly acetylated, and acetylation critically influences aberrant intracellular signaling pathways in asthma and COPD. The diverse set of selective and non-selective HDAC inhibitors used in pre-clinical models of airway inflammation show promising results, but several challenges still need to be overcome. One such challenge is the design of HDAC inhibitors with unique selectivity profiles, such as selectivity towards specific HDAC complexes. Novel strategies to disrupt HDAC complexes should be developed to validate HDACs further as targets for new anti-inflammatory pulmonary treatments.
Highlights
Inflammatory pulmonary diseases are among the most common health problems worldwide.Currently, approximately 339 million people suffer from asthma, which results in 250 thousand preventable deaths annually [1,2]
We aim to describe the molecular mechanisms in asthma and chronic obstructive pulmonary disease (COPD), wherein protein acetylation plays a key role
Recruitment binding protein that uses ATP to modify the chromatin structure is able to bind to the complex of the two copies of HDAC1/2 towards the complex is mediated by the dimeric ELM2-SANT
Summary
Inflammatory pulmonary diseases are among the most common health problems worldwide. Currently, approximately 339 million people suffer from asthma, which results in 250 thousand preventable deaths annually [1,2]. Acetylation of histones facilitates transcriptional activation either by neutralizing the ionic interaction between DNA and the histones or by forming a binding site for chromatin remodeling proteins and transcription factors [9,10]. Disruption of this process results in abnormal gene expression that contributes to the pathogenesis of asthma and COPD. We aim to describe the molecular mechanisms in asthma and COPD, wherein protein acetylation plays a key role. An important future challenge will be to develop tools that selectively interfere with HDAC complexes involved in inflammation
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