title: Inactivation of liver X receptor beta leads to adult-onset motor neuron degeneration in male mice.
abstract: 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.
authors.affiliation: Department of Medical Nutrition, Karolinska Institute, Novum, 141 86 Huddinge, Sweden.
authors.forename: Sandra
authors.initials: S
authors.lastname: Andersson
authors.forename: Nina
authors.initials: N
authors.lastname: Gustafsson
authors.forename: Margaret
authors.initials: M
authors.lastname: Warner
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12097-102
references.pmid: 11035776
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):266-71
references.pmid: 9874807
references.citation: J Neurol. 2000 Dec;247:2-6
references.pmid: 11200702
references.citation: J Clin Invest. 2001 Mar;107(5):565-73
references.pmid: 11238557
references.citation: J Biol Chem. 2001 Oct 19;276(42):38378-87
references.pmid: 11504730
references.citation: Nat Rev Neurosci. 2001 Nov;2(11):806-19
references.pmid: 11715057
references.citation: J Biol Chem. 2002 May 24;277(21):18793-800
references.pmid: 11901146
references.citation: Mol Endocrinol. 2002 Jun;16(6):1378-85
references.pmid: 12040022
references.citation: J Neurochem. 2002 Aug;82(3):516-28
references.pmid: 12153476
references.citation: Ann Neurol. 2002 Oct;52(4):448-57
references.pmid: 12325074
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13878-83
references.pmid: 12368482
references.citation: J Biol Chem. 2003 May 2;278(18):15565-70
references.pmid: 12601003
references.citation: J Biol Chem. 2003 Jun 20;278(25):22980-8
references.pmid: 12686551
references.citation: J Lipid Res. 2003 Sep;44(9):1780-9
references.pmid: 12810827
references.citation: Brain Res Dev Brain Res. 2003 Dec 19;146(1-2):87-98
references.pmid: 14643015
references.citation: J Lipid Res. 2004 Feb;45(2):301-7
references.pmid: 14657202
references.citation: Anat Rec A Discov Mol Cell Evol Biol. 2004 Apr;277(2):312-6
references.pmid: 15052659
references.citation: J Cell Biol. 1967 Jul;34(1):207-17
references.pmid: 6033532
references.citation: J Neuropathol Exp Neurol. 1977 Sep-Oct;36(5):853-60
references.pmid: 894328
references.citation: Acta Neuropathol. 1977 Nov 28;40(3):219-25
references.pmid: 602685
references.citation: Bioessays. 2003 Jan;25(1):72-8
references.pmid: 12508285
references.citation: Gene. 2000 Feb 8;243(1-2):93-103
references.pmid: 10675617
references.citation: Biochem Biophys Res Commun. 2000 Aug 11;274(3):794-802
references.pmid: 10924356
references.citation: Mech Ageing Dev. 1979 May;10(3-4):241-8
references.pmid: 88552
references.citation: Brain Res. 1980 Feb 10;183(2):477-80
references.pmid: 6153285
references.citation: J Neurol Sci. 1981 Jun;50(3):413-21
references.pmid: 7264705
references.citation: J Neuropathol Exp Neurol. 1981 Nov;40(6):667-75
references.pmid: 7299423
references.citation: J Lipid Res. 1985 Sep;26(9):1126-33
references.pmid: 4067433
references.citation: J Clin Invest. 1986 Jun;77(6):1864-72
references.pmid: 3711338
references.citation: J Nutr. 1991 Sep;121(9):1323-30
references.pmid: 1880610
references.citation: Anat Rec. 1991 Dec;231(4):482-97
references.pmid: 1793176
references.citation: Nature. 1993 Mar 4;362(6415):59-62
references.pmid: 8446170
references.citation: J Neurochem. 1995 Feb;64(2):895-901
references.pmid: 7830084
references.citation: J Neurochem. 1995 Nov;65(5):2299-306
references.pmid: 7595519
references.citation: Nat Genet. 1996 May;13(1):43-7
references.pmid: 8673102
references.citation: J Neurochem. 1996 May;66(5):1836-44
references.pmid: 8780008
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9799-804
references.pmid: 8790411
references.citation: J Mol Neurosci. 1996 Spring;7(1):29-39
references.pmid: 8835780
references.citation: Nature. 1996 Oct 24;383(6602):728-31
references.pmid: 8878485
references.citation: J Biol Chem. 1997 Feb 7;272(6):3137-40
references.pmid: 9013544
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1488-93
references.pmid: 9037080
references.citation: Science. 1997 Jul 11;277(5323):232-5
references.pmid: 9211850
references.citation: Acta Neuropathol. 1997 Aug;94(2):164-72
references.pmid: 9255392
references.citation: Am J Med. 1997 Sep 22;103(3A):11S-18S
references.pmid: 9344402
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10588-93
references.pmid: 9380679
references.citation: Trends Neurosci. 1998 Feb;21(2):53-7
references.pmid: 9498297
references.citation: Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5257-62
references.pmid: 10220453
references.citation: J Biol Chem. 1999 May 21;274(21):14624-31
references.pmid: 10329655
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7238-43
references.pmid: 10377398
references.citation: Science. 2000 Dec 22;290(5500):2298-301
references.pmid: 11125141
references.citation: Cell. 1998 May 29;93(5):693-704
references.pmid: 9630215
references.citation: J Clin Invest. 1998 Sep 1;102(5):910-8
references.pmid: 9727059