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Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases?
- 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.
- Subjects :
- amyotrophic lateral sclerosis
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Review
Ligands
multiple sclerosis
Liver X receptors
neuroinflammation
lcsh:Chemistry
Myelin
0302 clinical medicine
Medicine
Homeostasis
lcsh:QH301-705.5
Spectroscopy
0303 health sciences
Brain
Neurodegenerative Diseases
General Medicine
Alzheimer's disease
Computer Science Applications
medicine.anatomical_structure
oxysterols
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
lipids (amino acids, peptides, and proteins)
Disease Susceptibility
Alzheimer’s disease
Oxysterol
Central nervous system
Neuroprotection
Catalysis
Inorganic Chemistry
03 medical and health sciences
Structure-Activity Relationship
Animals
Humans
[CHIM]Chemical Sciences
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Physical and Theoretical Chemistry
Liver X receptor
Molecular Biology
Neuroinflammation
030304 developmental biology
business.industry
Multiple sclerosis
Organic Chemistry
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
cholesterol
medicine.disease
Lipid Metabolism
lcsh:Biology (General)
lcsh:QD1-999
Nuclear receptor
business
Neuroscience
030217 neurology & neurosurgery
Subjects
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