Authors: Roth, M.; Black, J. L.

Source: Current Drug Targets, Volume 7, Number 5, May 2006 , pp. 589-595(7)

Publisher: Bentham Science Publishers

Abstract:

The essential features of persistent severe asthma include structural changes in the airway wall (remodelling). It is not known whether these are the sequelae of chronic inflammation or indeed its initiators. Several transcription factors have been implicated in the inflammatory process in asthma, including the glucocorticoid receptor (GR), NFκB, Activator Protein-1 (AP-1), Nuclear Factor of Activated T-cells (NF-AT), cyclic AMP Response Element Binding Protein and more recently, the CCAAT/Enhancer Binding Protein (C/EBP), Peroxisome Proliferator-activated Receptor (PPAR) and the bZIP transcription factor, Nrf2. Could a pathological de-regulation of one of these transcription factors explain the broad spectrum of asthma pathology and can their modulation lead to better symptom control?

Although some of the transcription factors seem to be valid targets (NFkB, Nrf2 or STAT6) or tools (PPARγ, -α and C/EBP-α) for new therapeutic approaches, since many transcription factors play a central role in tissue and organ homeostasis, a longterm general suppression or overexpression, would cause severe side effects in other organs.

Cell type specific application of decoy or antisense oligonucleotides for NFκB, Nrf2 or STAT6, or specific agonists for PPARγ and -α may help to control the inflammatory response in lung epithelial cells and infiltrated immune cells, but additional, unwanted, effects on other resident cells of the lung cannot be excluded and a beneficial effect over known antiasthma drugs has first to be proven. In order to progress with such novel therapeutic strategies, the only option seems to be to link transcription factor inhibitors/activators to a cell type specific delivery system.

Keywords: asthma; airway remodelling; airway smooth muscle; transcription factors; asthma therapy

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138945006776818638

Affiliations: 1: Department Pharmacology, Respiratory Research Group, University of Sydney, NSW-2006 Sydney and The Woolcock Institute for Medical Research, NSW-2050 Camperdown, Australia.

Publication date: 2006-05-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

Related content

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Roth, M. ;  Black, J. L.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers