Inactivation of liver X receptor beta leads to adult-onset motor neuron degeneration in male mice.
Male mice with inactivated liver X receptor (LXR) beta suffer from adult-onset motor neuron degeneration. By 7 months of age, motor coordination is impaired, and this condition is associated with lipid accumulation and loss of motor neurons in the spinal cord, together with axonal atrophy and astrogliosis. Several of these features are reminiscent of the neuropathological signs of chronic motor neuron disease such as amyotrophic lateral sclerosis. Because the LXRs are important for cholesterol and lipid metabolism, we speculate that absence of LXRbeta leads to pathological accumulation of sterols and lipids that may themselves be neurotoxic or may modulate intracellular pathways and thereby predispose motor neurons to degeneration.
Andersson
Sandra
S
Department of Medical Nutrition, Karolinska Institute, Novum, 141 86 Huddinge, Sweden.
Gustafsson
Nina
N
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
D000690:Amyotrophic Lateral Sclerosis; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001369:Axons / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016472:Motor Neuron Disease / Q000209:etiology* / Q000473:pathology; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*
D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol
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