PPARs: history and advances.

Peroxisome proliferator-activated receptors (PPARs) are members of the steroid hormone receptor superfamily, discovered in 1990. To date, three PPAR subtypes have been identified; PPARα, PPAR ß/δ, and PPARγ. These receptors share a high degree of homology but differ in tissue distribution and ligand specificity. PPARs have been implicated in the etiology as well as treatment of several important diseases and pathological conditions such as diabetes, inflammation, senescence-related diseases, regulation of fertility, and various types of cancer. Consequently, significant efforts to discover novel PPAR roles and delineate molecular mechanisms involved in their activation and repression as well as develop safer and more effective PPAR modulators, as therapeutic agents to treat a myriad of diseases and conditions, are underway. This volume of Methods in Molecular Biology contains details of experimental protocols used in researching these receptors.

Fibrates, glitazones, and peroxisome proliferator-activated receptors.

Several decades ago, fibrates were approved for the treatment of dyslipidemia, whereas thiazolidinediones were screened in animal models to improve glucose homeostasis and were subsequently developed for the treatment of type 2 diabetes mellitus. Relatively recently, these drugs were found to act via peroxisome proliferator-activated receptors, nuclear receptors that control lipid metabolism and glucose homeostasis. In this historical perspective, we discuss the history of discovery of the peroxisome proliferator-activated receptors, from the clinical development of their agonists to the subsequent discovery of these receptors and their mechanisms of action, to finally evoke possibilities of targeted pharmacology for future development of selective peroxisome proliferator-activated receptor modulators.