Acetylation and Methylation in Asthma, COPD, and Lung Cancer

The urgent need for new therapies to treat airway inflammatory diseases is exemplified by the death of approximately 3 million patients suffering from chronic obstructive pulmonary disease (COPD) each year. Deranged intracellular signaling pathways in COPD, and in asthma alike, are critically regulated by protein posttranslational modifications (PTMs). Acetylation is one of the quintessential PTMs, found on over a thousand proteins and influencing a diverse range of protein properties. Firstly discovered on histones, their acetylation leads to a decrease in DNA-binding affinity and a concomitant increase in gene expression. Acetyltransferases and deacetylases, the enzymes that control acetylation, have been recognized as important drug targets and many deacetylase inhibitors have hence been developed. The deacetylase inhibitors that are currently evaluated in asthma and COPD show actions that go way beyond regulation of epigenetic mechanisms and inflammation, with deacetylase inhibitors even acting on airway smooth muscle contraction and motility. Distinct deacetylase isoforms are at play in each disease and potent isoform selective deacetylase inhibitors are thus highly needed and promising steps have been made in their development