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lüll The nuclear hormone receptor PPARgamma as a therapeutic target in major diseases Schmidt MV; Brune B; von Knethen AScientificWorldJournal 2010[Nov]; 10 (ä): 2181-97The peroxisome proliferator-activated receptor gamma (PPARgamma 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, PPARgamma was identified as being essential for glucose metabolism. Thus, synthetic PPARgamma 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 PPARgamma in controlling various diseases based on its anti-inflammatory, cell cycle arresting, and proapoptotic properties. In this regard, expression of PPARgamma 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 PPARgamma in lymphoid organs and its modulation of macrophage inflammatory responses, lymphocyte proliferation, cytokine production, and apoptosis underscore its immune regulating functions. Moreover, PPARgamma expression is found in tumor cells, where its activation facilitates antitumorigenic actions. This review provides an overview about the role of PPARgamma as a possible therapeutic target approaching major, severe diseases, such as sepsis, cancer, and atherosclerosis.|Animals[MESH]|Atherosclerosis/drug therapy/metabolism[MESH]|Diabetes Mellitus, Type 2/drug therapy/metabolism[MESH]|Humans[MESH]|Models, Biological[MESH]|Neoplasms/drug therapy/metabolism[MESH]|PPAR gamma/agonists/*metabolism[MESH]|Receptors, Cytoplasmic and Nuclear/agonists/*metabolism[MESH]|Sepsis/drug therapy/metabolism[MESH]|Thiazolidinediones/therapeutic use[MESH] |