title: Liver X receptors: from cholesterol regulation to neuroprotection-a new barrier against neurodegeneration in amyotrophic lateral sclerosis?
abstract: Cholesterol plays a central role in numerous nervous system functions. Cholesterol is the major constituent of myelin sheaths, is essential for synapse and dendrite formation, axon guidance as well as neurotransmission. Among regulators of cholesterol homeostasis, liver X receptors (LXRs), two members of the nuclear receptor superfamily, play a determinant role. LXRs act as cholesterol sensors and respond to high intracellular cholesterol concentration by decreasing plasmatic and intracellular cholesterol content. Beyond their cholesterol-lowering role, LXRs have been proposed as regulators of immunity and anti-inflammatory factors. Dysregulation of cholesterol metabolism combined to neuroinflammatory context have been described in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). ALS is characterized by the progressive loss of motoneurons in the brain and spinal cord, leading to severe paralytic condition and death of patients in a median time of 3 years. Motoneuron degeneration is accompanied by chronic neuroinflammatory response, involving microglial and astrocytic activation, infiltration of blood-derived immune cells and release of pro-inflammatory factors. We propose to discuss here the role of LXRs as a molecular link between the central nervous system cholesterol metabolism, neuroinflammation, motoneuron survival and their potential as promising therapeutic candidates for ALS therapy.
authors: Department of Biochemistry and Molecular Biology, Nîmes University Hospital, Nîmes, France. kevin.mouzat@umontpellier.fr.|University of Montpellier, Montpellier, France. kevin.mouzat@umontpellier.fr.|INSERM UMR1051, The Neuroscience Institute of Montpellier (INM), Saint Eloi Hospital, Montpellier, France. kevin.mouzat@umontpellier.fr.
authors: Kevin
authors: K
authors: Mouzat
authors: INSERM UMR1051, The Neuroscience Institute of Montpellier (INM), Saint Eloi Hospital, Montpellier, France.
authors: Cédric
authors: C
authors: Raoul
authors: Department of Biochemistry and Molecular Biology, Nîmes University Hospital, Nîmes, France.
authors: Anne
authors: A
authors: Polge
authors: Department of Biochemistry and Molecular Biology, Nîmes University Hospital, Nîmes, France.|INSERM UMR1051, The Neuroscience Institute of Montpellier (INM), Saint Eloi Hospital, Montpellier, France.
authors: Jovana
authors: J
authors: Kantar
authors: University of Montpellier, Montpellier, France.|INSERM UMR1051, The Neuroscience Institute of Montpellier (INM), Saint Eloi Hospital, Montpellier, France.|Neurology Department, ALS Center, Gui de Chauliac Hospital, Montpellier, France.
authors: William
authors: W
authors: Camu
authors: Department of Biochemistry and Molecular Biology, Nîmes University Hospital, Nîmes, France.|University of Montpellier, Montpellier, France.|INSERM UMR1051, The Neuroscience Institute of Montpellier (INM), Saint Eloi Hospital, Montpellier, France.
authors: Serge
authors: S
authors: Lumbroso
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D000071518:Liver X Receptors / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology*; D000066829:Neuroprotection
chemical_list: D000071518:Liver X Receptors; D002784:Cholesterol
keywords: Amyotrophic lateral sclerosis; Astrocytes; Cholesterol; Liver X receptors; Microglia; Neuroinflammation