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Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases?

Authors :
Anne Polge
Serge Lumbroso
Aleksandra V Chudinova
Jovana Kantar
Cédric Raoul
Kevin Mouzat
William Camu
Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM)
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Laboratoire de Biochimie [CHRU Nîmes]
Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Raoul, Cédric
Institut des Neurosciences de Montpellier (INM)
Source :
International Journal of Molecular Sciences, International Journal of Molecular Sciences, MDPI, 2019, 20 (16), pp.3858. ⟨10.3390/ijms20163858⟩, International Journal of Molecular Sciences, Vol 20, Iss 16, p 3858 (2019)
Publication Year :
2019
Publisher :
HAL CCSD, 2019.

Abstract

International audience; 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.

Details

Language :
English
ISSN :
16616596 and 14220067
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences, International Journal of Molecular Sciences, MDPI, 2019, 20 (16), pp.3858. ⟨10.3390/ijms20163858⟩, International Journal of Molecular Sciences, Vol 20, Iss 16, p 3858 (2019)
Accession number :
edsair.doi.dedup.....3dfb411e562e7c8c07202d081bfb9489