Targeting HDAC Complexes in Asthma and COPD

被引:41
|
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
相关论文
共 50 条
  • [1] Epigenetics in asthma and COPD
    Kabesch, Michael
    Adcock, Ian M.
    BIOCHIMIE, 2012, 94 (11) : 2231 - 2241
  • [2] The Relevance of Targeting Treatment to Small Airways in Asthma and COPD
    Santus, Pierachille
    Radovanovic, Dejan
    Pecchiari, Matteo
    Ferrando, Matteo
    Tursi, Francesco
    Patella, Vincenzo
    Braido, Fulvio
    RESPIRATORY CARE, 2020, 65 (09) : 1392 - 1412
  • [3] Asthma and COPD
    Welte, Tobias
    Groneberg, David A.
    EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, 2006, 57 : 35 - 40
  • [4] Metabolomics of asthma, COPD, and asthma-COPD overlap: an overview
    Dasgupta, Sanjukta
    Ghosh, Nilanjana
    Bhattacharyya, Parthasarathi
    Chowdhury, Sushmita Roy
    Chaudhury, Koel
    CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 2023, 60 (02) : 153 - 170
  • [5] Combination Therapies Targeting HDAC and IKK in Solid Tumors
    Vancurova, Ivana
    Uddin, Mohammad M.
    Zou, Yue
    Vancura, Ales
    TRENDS IN PHARMACOLOGICAL SCIENCES, 2018, 39 (03) : 295 - 306
  • [6] Challenges in targeting TNFα in asthma and COPD
    Antoniu, Sabina A.
    CURRENT OPINION IN INVESTIGATIONAL DRUGS, 2009, 10 (05) : 404 - 406
  • [7] Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes
    Bantscheff, Marcus
    Hopf, Carsten
    Savitski, Mikhail M.
    Dittmann, Antje
    Grandi, Paola
    Michon, Anne-Marie
    Schlegl, Judith
    Abraham, Yann
    Becher, Isabelle
    Bergamini, Giovanna
    Boesche, Markus
    Delling, Manja
    Duempelfeld, Birgit
    Eberhard, Dirk
    Huthmacher, Carola
    Mathieson, Toby
    Poeckel, Daniel
    Reader, Valerie
    Strunk, Katja
    Sweetman, Gavain
    Kruse, Ulrich
    Neubauer, Gitte
    Ramsden, Nigel G.
    Drewes, Gerard
    NATURE BIOTECHNOLOGY, 2011, 29 (03) : 255 - U124
  • [8] Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53
    Mrakovcic, Maria
    Bohner, Lauren
    Hanisch, Marcel
    Froehlich, Leopold F.
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (12)
  • [9] Mechanisms of Corticosteroid Resistance in Severe Asthma and Chronic Obstructive Pulmonary Disease (COPD)
    Adcock, Ian M.
    Marwick, John
    Casolari, Paolo
    Contoli, Marco
    Chung, Kian Fan
    Kirkham, Paul
    Papi, Alberto
    Caramori, Gaetano
    CURRENT PHARMACEUTICAL DESIGN, 2010, 16 (32) : 3554 - 3573
  • [10] Role of Transcription Factors in the Pathogenesis of Asthma and COPD
    Caramori, Gaetano
    Casolari, Paolo
    Adcock, Ian
    CELL COMMUNICATION AND ADHESION, 2013, 20 (1-2) : 21 - 40