Targeting HDAC Complexes in Asthma and COPD

被引:42
作者
Zwinderman, Martijn R. H. [1 ]
de Weerd, Sander [1 ]
Dekker, Frank J. [1 ]
机构
[1] Univ Groningen, GRIP, Dept Chem & Pharmaceut Biol, NL-9713 AV Groningen, Netherlands
关键词
asthma; COPD; inflammation; NF-kappa B; HDAC; acetylation; post translational modification (PTM); inhibitor; drug design; co-repressor complex; review; HISTONE DEACETYLASE INHIBITORS; NF-KAPPA-B; GLUCOCORTICOID-RECEPTOR-BETA; GENE-EXPRESSION PROGRAM; TRANSCRIPTIONAL REPRESSION; CORTICOSTEROID RESISTANCE; COREPRESSOR COMPLEX; STRUCTURAL BASIS; PROSTATE-CANCER; BREAST-CANCER;
D O I
10.3390/epigenomes3030019
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页数:25
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