Lipid metabolism and neuroinflammation in Alzheimer's disease: a role for liver X receptors

Endocr Rev. 2012 Oct;33(5):715-46. doi: 10.1210/er.2011-1049. Epub 2012 Jul 5.

Abstract

Liver X receptors (LXR) are nuclear receptors that have emerged as key regulators of lipid metabolism. In addition to their functions as cholesterol sensors, LXR have also been found to regulate inflammatory responses in macrophages. Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive cognitive decline associated with inflammation. Evidence indicates that the initiation and progression of AD is linked to aberrant cholesterol metabolism and inflammation. Activation of LXR can regulate neuroinflammation and decrease amyloid-β peptide accumulation. Here, we highlight the role of LXR in orchestrating lipid homeostasis and neuroinflammation in the brain. In addition, diabetes mellitus is also briefly discussed as a significant risk factor for AD because of the appearing beneficial effects of LXR on glucose homeostasis. The ability of LXR to attenuate AD pathology makes them potential therapeutic targets for this neurodegenerative disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / immunology
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Cholesterol / metabolism*
  • Humans
  • Inflammation / complications
  • Inflammation / metabolism*
  • Liver X Receptors
  • Orphan Nuclear Receptors / immunology
  • Orphan Nuclear Receptors / metabolism*

Substances

  • Amyloid beta-Peptides
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Cholesterol