Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
Receptor Research Laboratories, Nuclear Receptor Laboratory, VIB Center for Medical Biotechnology, Ghent, Belgium.
Endocr Rev. 2018 Oct 1;39(5):760-802. doi: 10.1210/er.2018-00064.
Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor of clinical interest as a drug target in various metabolic disorders. PPARα also exhibits marked anti-inflammatory capacities. The first-generation PPARα agonists, the fibrates, have however been hampered by drug-drug interaction issues, statin drop-in, and ill-designed cardiovascular intervention trials. Notwithstanding, understanding the molecular mechanisms by which PPARα works will enable control of its activities as a drug target for metabolic diseases with an underlying inflammatory component. Given its role in reshaping the immune system, the full potential of this nuclear receptor subtype as a versatile drug target with high plasticity becomes increasingly clear, and a novel generation of agonists may pave the way for novel fields of applications.
过氧化物酶体增殖物激活受体 α(PPARα)是一种核受体,具有临床意义,可作为各种代谢紊乱的药物靶点。PPARα 还具有显著的抗炎能力。然而,第一代 PPARα 激动剂,即贝特类药物,由于药物相互作用问题、他汀类药物的替代以及设计不当的心血管干预试验而受到阻碍。尽管如此,了解 PPARα 发挥作用的分子机制将使其能够作为具有潜在炎症成分的代谢疾病的药物靶点来控制其活性。鉴于其在重塑免疫系统方面的作用,这种核受体亚型作为一种具有高度可塑性的多功能药物靶点的全部潜力变得越来越明显,新一代激动剂可能为新的应用领域铺平道路。