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Mitochondrial Dysfunction by Synthetic Ligands of Peroxisome Proliferator Activated Receptors (PPARs)
Author(s) -
Scatena Roberto,
Martorana Giuseppe,
Bottoni Patrizia,
Giardina Bruno
Publication year - 2004
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540400008416
Subject(s) - peroxisome proliferator activated receptor , receptor , ppar agonist , nuclear receptor , lipid metabolism , peroxisome , pharmacology , biology , chemistry , biochemistry , transcription factor , gene
PPARs are a class of nuclear receptors involved in lipid and glucidic metabolism, immune regulation and cell differentiation. This spectrum of biological activities stimulated pharmacological research to synthetize different molecules with PPARs binding activity with beneficial therapeutic effects. As a matter of fact, some synthetic PPAR‐ligands have been already employed in pharmacotherapy: PPAR‐α ligands, such as fibrates, are used in hyperlipidemias and thiazolidinediones, mainly PPAR‐γ ligands, are employed as insulin sensitizers. However, both classes of drugs showed pharmacotoxicological profiles which cannot be fully ascribed to activation of their specific receptors and which are causing a growing incidence of dramatic side effects (rhabdomyolysis, acute liver failure, heart failure, etc.). A re‐evaluation of the biological activities of PPAR synthetic ligands, in particular of the mitochondrial dysfunction based on a rotenone‐like Complex I partial inhibition and of its consequent metabolic adaptations, seems to explain some of the pathophysiologic aspects of PPARs allowing a better definition of the therapeutic properties of the so‐called PPAR‐ligands. IUBMB Life, 56: 477‐482, 2004