The Nuclear Hormone Receptor PPAR_γ as a Therapeutic Target in Major Diseases

Abstract

The peroxisome proliferator-activated receptor γ (PPAR_γ) belongs to the nuclear hormone receptor superfamily and regulates gene expression upon heterodimerization with the retinoid X receptor by ligating to peroxisome proliferator response elements (PPREs) in the promoter region of target genes. Originally, PPAR_γ was identified as being essential for glucose metabolism. Thus, synthetic PPAR_γ agonists, the thiazolidinediones (TZDs), are used in type 2 diabetes therapy as insulin sensitizers. More recent evidence implied an important role for the nuclear hormone receptor PPAR_γ in controlling various diseases based on its anti-inflammatory, cell cycle arresting, and proapoptotic properties. In this regard, expression of PPAR_γ is not restricted to adipocytes, but is also found in immune cells, such as B and T lymphocytes, monocytes, macrophages, dendritic cells, and granulocytes. The expression of PPAR_γ in lymphoid organs and its modulation of macrophage inflammatory responses, lymphocyte proliferation, cytokine production, and apoptosis underscore its immune regulating functions. Moreover, PPAR_γ expression is found in tumor cells, where its activation facilitates antitumorigenic actions. This review provides an overview about the role of PPAR_γ as a possible therapeutic target approaching major, severe diseases, such as sepsis, cancer, and atherosclerosis.