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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

New Pharmacological Perspectives and Therapeutic Potential of PPAR-γ Agonists

Author(s): C. Alarcon de la Lastra, S. Sanchez-Fidalgo, I. Villegas and V. Motilva

Volume 10, Issue 28, 2004

Page: [3505 - 3524] Pages: 20

DOI: 10.2174/1381612043382909

Price: $65

Abstract

The peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear hormone receptor superfamily has classically been characterized for its implications in adipocyte differentiation and fat metabolism. Recently, PPARg has been implicated in the pathophysiology of inflammatory and immune responses possibly through inhibition of the mitogen-activated protein kinase (MAPK) pathways or the activation of the transcription nuclear factor kappa B (NF-κB). Thus, these agents might also have therapeutic potential in the treatment of gastrointestinal inflammatory disorders, such as ulcerative colitis and Crohns disease. The synthetic thiazolidinediones (TZDs), a novel class of insulin-sensitizing drugs, were the first class of compounds identified as PPARγ ligands, and represent a significant advance in anti-diabetic therapy. However, there is less information about endogenous ligands, although the prostaglandin (PG)J2 and the oxidized phosphatidylcholine have been suggested. Furthermore, PPARg ligands have been shown to be potent inhibitors of angiogenesis, a process necessary for tumor growth and metastasis, and protect against cellular transformation. Further work is needed to establish in detail the anti-proliferative and pro-differentiation mechanisms of PPARγ activators and their efficacy in certain cancers.

Keywords: pparg, thiazolidinedione, inflammation, diabetes, cancer


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