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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR)

Marjorie A Peraza1, Andrew D Burdick, Holly E Marin

  • 1Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|December 3, 2005
PubMed

Insights

Peroxisome proliferator-activated receptors (PPARs) are transcription factors targeted by drugs for diseases like diabetes. Understanding PPAR ligand toxicity mechanisms is crucial, as receptor-dependent and off-target effects remain unclear.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Toxicology

Background:

  • Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate gene expression.
  • PPAR ligands are developed for treating metabolic diseases like dyslipidemia and diabetes.
  • PPAR ligand therapy can cause toxicities, with unclear mechanisms.

Purpose of the Study:

  • To discuss the toxicities and mechanisms of PPAR ligands.
  • To highlight data gaps in understanding PPAR ligand-induced toxicity.
  • To differentiate receptor-dependent from off-target toxicity mechanisms.

Main Methods:

  • Literature review of PPAR ligand toxicity.
  • Analysis of receptor-dependent and off-target mechanisms.
  • Evaluation of data extrapolation from animal/in vitro models to humans.

Main Results:

  • PPAR ligands exhibit various toxicities.
  • Mechanisms of toxicity can be receptor-dependent or off-target.
  • Extrapolation of animal/in vitro data to humans is challenging.

Conclusions:

  • Further research is needed to clarify PPAR ligand toxicity mechanisms.
  • Addressing data gaps will improve the safe use of PPAR-targeting drugs.
  • Distinguishing between direct and indirect toxic effects is critical for therapeutic development.

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