Authors: Tas, Sander W.; Remans, Philip H.J.; Reedquist, Kris A.; Tak, Paul P.

Source: Current Pharmaceutical Design, Volume 11, Number 5, February 2005 , pp. 581-611(31)

Publisher: Bentham Science Publishers

Abstract:

Many chronic inflammatory diseases are associated with deregulated intracellular signal transduction pathways. Resultant pathogenic interactions between immune and stromal cells lead to changes in cell activation, proliferation, migratory capacity, and cell survival that all contribute to inflammation. Increasing efforts are now being made in the design of novel therapeutic compounds to interfere with signaling pathways in inflammatory diseases like rheumatoid arthritis (RA). In this review we will outline the major signal transduction pathways involved in the pathogenesis of RA. We will assess advances in targeting a number of key intracellular pathways, including nuclear factor-B (NF-B), mitogen-associated protein kinases (MAPKs), phosphoinositide 3-kinase (PI3K) / Akt, signal transducers and activators of transcription (STATs), and reactive oxygen species (ROS) production. Finally, we will discuss recently identified lead molecules and the progress of selected compounds towards becoming new drugs for the treatment of inflammatory diseases.

Keywords: inflammatory disease; rheumatoid arthritis; signal transduction; nuclear factor; mitogen-activated protein kinase; reactive oxygen species; novel therapies

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612053381918

Affiliations: 1: Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, the Netherlands.

Publication date: 2005-02-01

More about this publication?

• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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