New pharmacological perspectives and therapeutic potential of PPAR-gamma agonists

Curr Pharm Des. 2004;10(28):3505-24. doi: 10.2174/1381612043382909.


The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily has classically been characterized for its implications in adipocyte differentiation and fat metabolism. Recently, PPARgamma 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-kappaB). Thus, these agents might also have therapeutic potential in the treatment of gastrointestinal inflammatory disorders, such as ulcerative colitis and Crohn's disease. The synthetic thiazolidinediones (TZDs), a novel class of insulin-sensitizing drugs, were the first class of compounds identified as PPARgamma ligands, and represent a significant advance in anti-diabetic therapy. However, there is less information about endogenous ligands, although the prostaglandin (PG)J(2) and the oxidized phosphatidylcholine have been suggested. Furthermore, PPARgamma 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 PPARgamma activators and their efficacy in certain cancers.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / drug therapy
  • Digestive System Diseases / drug therapy
  • Digestive System Diseases / metabolism
  • Humans
  • Insulin Resistance / physiology
  • Ligands
  • PPAR gamma / agonists*
  • PPAR gamma / genetics


  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antirheumatic Agents
  • Ligands
  • PPAR gamma