Targeting HDAC Complexes in Asthma and COPD

Martijn R. H. Zwinderman, Sander de Weerd, Frank J. Dekker*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

38 Citations (Scopus)
236 Downloads (Pure)

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.

Original languageEnglish
Article number19
Number of pages25
JournalEpigenomes
Volume3
Issue number3
DOIs
Publication statusPublished - 7-Sept-2019

Keywords

  • 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

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