Signal Transduction Pathways and Transcription Factors as Therapeutic Targets in Inflammatory Disease: Towards Innovative Antirheumatic Therapy
Authors: Tas, Sander W.1; Remans, Philip H.J.1; Reedquist, Kris A.1; Tak, Paul P.1
Source: Current Pharmaceutical Design, Volume 11, Number 5, February 2005 , pp. 581-611(31)
Publisher: Bentham Science Publishers
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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: 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.
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