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

International Journal of Molecular Sciences

William Camu¹  Anne Polge²  Jovana Kantar³  Serge Lumbroso³  Kevin Mouzat³  Aleksandra Chudinova³  Cédric Raoul⁴ 

[1] ALS Reference Center, Montpellier University Hospital and University of Montpellier, Inserm UMR1051, 34000 Montpellier, France;Laboratoire de Biochimie et Biologie Moléculaire, Nimes University Hospital, University of Montpellier, 30029 Nîmes, France;Motoneuron Disease: Pathophysiology and Therapy, The Neuroscience Institute of Montpellier, University of Montpellier, Montpellier, Laboratoire de Biochimie et Biologie Moléculaire, Nimes University Hospital, 30029 Nîmes, France;The Neuroscience Institute of Montpellier, Inserm UMR1051, University of Montpellier, 34091 Montpellier, France;

关键词: Liver X receptors;    cholesterol;    oxysterols;    neuroinflammation;    amyotrophic lateral sclerosis;    Alzheimer’s disease;    multiple sclerosis;   

DOI  :  10.3390/ijms20163858

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown