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Oxysterols and nuclear receptors

Liqian Ma1, Erik R Nelson2

  • 1Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL, United States.

Molecular and Cellular Endocrinology
|January 21, 2019
PubMed

Insights

Oxysterols, cholesterol metabolites, regulate cholesterol and immune responses by engaging nuclear receptors. Their multifaceted roles impact diseases like cancer and Alzheimer's, necessitating targeted therapeutic strategies.

Area of Science:

  • Biochemistry and Molecular Biology
  • Immunology
  • Endocrinology

Background:

  • Oxysterols are cholesterol derivatives crucial for cholesterol metabolism.
  • They act as ligands for various nuclear receptors, including liver X receptors (LXRs).
  • Oxysterols also interact with RAR-related orphan receptors (RORs), influencing T cell differentiation.

Purpose of the Study:

  • To review recent advancements in oxysterol research.
  • To highlight oxysterol functions mediated by nuclear receptors (LXRs, estrogen receptors, RORs, glucocorticoid receptor).
  • To discuss the impact of oxysterol-nuclear receptor interactions on immune regulation and disease progression.

Main Methods:

  • Literature review of recent developments in oxysterol research.
  • Analysis of oxysterol interactions with multiple nuclear receptors.
  • Examination of oxysterol roles in immune cells (macrophages, T cells) and disease models.

Main Results:

  • Oxysterols modulate immune functions, including macrophage pro-inflammatory activity and T cell development.
  • Oxysterol-nuclear receptor interactions are implicated in diseases such as cancer, Alzheimer's disease, and atherosclerosis.
  • Evidence suggests selective modulation of nuclear receptors by oxysterols is key to their diverse biological effects.

Conclusions:

  • Oxysterols play significant roles in cholesterol metabolism, immune regulation, and disease pathogenesis.
  • Their effects are mediated through complex interactions with multiple nuclear receptors.
  • Understanding these multifaceted roles is essential for developing targeted therapeutic interventions.
Keywords:
27-HydroxycholesterolBreast cancerCholesterolEstrogen receptorLiver x receptorOxysterolSelective estrogen receptor modulatorSelective nuclear receptor modulator

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