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Concept
Peroxisome proliferator-activated receptor
Summary
In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms.
Three types of PPARs have been identified: alpha, gamma, and delta (beta):
α (alpha) - expressed in liver, kidney, heart, muscle, adipose tissue, and others
β/δ (beta/delta) - expressed in many tissues, especially in brain, adipose tissue, and skin
γ (gamma) - although transcribed by the same gene, this PPAR, by way of alternative splicing, is expressed in three forms:
γ1 - expressed in virtually all tissues, including heart, muscle, colon, kidney, pancreas, and spleen
γ2 - expressed mainly in adipose tissue; it is 30 amino acids longer than γ1
γ3 - expressed in macrophages, large intestine, white adipose tissue
These agents, pharmacologically related to the fibrates were discovered in the early 1980s.
PPARs were originally identified in Xenopus frogs as receptors that induce the proliferation of peroxisomes in cells in 1992.
The first PPAR (PPARα) was discovered in 1990 during the search for a molecular target of a group of agents then referred to as peroxisome proliferators, as they increased peroxisomal numbers in rodent liver tissue, apart from improving insulin sensitivity.
When it turned out that PPARs played a much more versatile role in biology, the agents were in turn termed PPAR ligands. The best-known PPAR ligands are the thiazolidinediones.
After PPARδ (delta) was identified in humans in 1992, it turned out to be closely related to PPARβ (beta), previously described during the same year in an amphibian, Xenopus. The term "PPARδ" is generally used in the US, whereas the use of "PPARβ" has remained in Europe, where this receptor was initially discovered in Xenopus.
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