Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/ijms20163858
Keywords
Liver X receptors; cholesterol; oxysterols; neuroinflammation; amyotrophic lateral sclerosis; Alzheimer's disease; multiple sclerosis
Funding
- institut national de la sante et de la recherche medicale (Inserm)
- Groupement de Cooperation Sanitaire Montpellier-Nimes (GCS-MERRI)
- Association Francaise pour la Recherche sur la SLA (ARSLA)
- University Hospital of Nimes call for internal bids Thematiques emergentes
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Liver X Receptors (LXR) alpha and beta are two members of nuclear receptor superfamily documented as endogenous cholesterol sensors. Following conversion of cholesterol in oxysterol, both LXR isoforms detect intracellular concentrations and act as transcription factors to promote expression of target genes. Among their numerous physiological roles, they act as central cholesterol-lowering factors. In the central nervous system (CNS), cholesterol has been shown to be an essential determinant of brain function, particularly as a major constituent of myelin and membranes. In the brain, LXRs act as cholesterol central regulators, and, beyond this metabolic function, LXRs have additional roles such as providing neuroprotective effects and lowering neuroinflammation. In many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and multiple sclerosis (MS), dysregulations of cholesterol and oxysterol have been reported. In this paper, we propose to focus on recent advances in the knowledge of the LXRs roles on brain cholesterol and oxysterol homeostasis, neuroinflammation, neuroprotection, and their putative involvement in neurodegenerative disorders. We will discuss their potential use as candidates for both molecular diagnosis and as promising pharmacological targets in the treatment of ALS, AD, or MS patients.
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