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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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Published on: November 15, 2013

Nuclear receptors as drug targets for metabolic disease

Ira G Schulman1

  • 1Center for Molecular Design and Department of Pharmacology, University of Virginia Health System, 1340 Jefferson Park Avenue, Charlottesville, VA 22908, USA. igs4c@virginia.edu

Advanced Drug Delivery Reviews
|July 27, 2010
PubMed

Insights

Nuclear hormone receptors regulate metabolism by sensing metabolic intermediates or protein interactions. Understanding these nuclear receptors is key for developing new drugs targeting metabolic diseases.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Metabolic Regulation

Background:

  • Nuclear hormone receptors are crucial ligand-activated transcription factors.
  • They play vital roles in development, differentiation, and homeostasis.
  • Recent research highlights their role in regulating lipid metabolism and energy utilization.

Purpose of the Study:

  • To discuss the mechanisms by which nuclear hormone receptors impact metabolism.
  • To explore how these receptors sense metabolic activity.
  • To highlight challenges in developing drugs targeting these nuclear receptors.

Main Methods:

  • Review of scientific literature on nuclear hormone receptors and metabolism.
  • Analysis of known mechanisms of metabolic sensing by nuclear receptors.
  • Discussion of drug discovery challenges for nuclear receptor targets.

Main Results:

  • Nuclear receptors regulate metabolic pathways by directly sensing metabolites (e.g., fatty acids, cholesterol derivatives).
  • Some receptors sense metabolic activity indirectly through protein-protein interactions.
  • These receptors control the synthesis, transport, and breakdown of key metabolites.

Conclusions:

  • Nuclear hormone receptors are central regulators of metabolic processes.
  • Diverse mechanisms are employed by these receptors to sense and respond to metabolic cues.
  • Targeting nuclear receptors presents significant challenges for drug discovery in metabolic diseases.

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