Open AccessInactivation of liver X receptor β leads to adult-onset motor neuron degeneration in male mice
Author(s) -
Sandra Andersson,
Nina Gustafsson,
Margaret Warner,
Jan Åke Gustafsson
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0500634102
Subject(s) - motor neuron , amyotrophic lateral sclerosis , astrogliosis , liver x receptor , spinal cord , biology , degeneration (medical) , neuron , neuroscience , neurodegeneration , lipid metabolism , medicine , endocrinology , pathology , central nervous system , disease , nuclear receptor , biochemistry , gene , transcription factor
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.