Abstract
Alpha-synuclein is a lipid-binding protein expressed in neurons and oligodendrocytes which is increased in Parkinson's disease. We identified two putative liver X receptor (LXR) response elements in the human alpha-synuclein gene and used synthetic (TO901317, GW3695) and physiological (27-hydroxycholesterol) LXR activators to assess regulation of alpha-synuclein. LXR ligands upregulated alpha-synuclein mRNA by two-five-fold in human SK-N-SH neurons and three-six-fold in human MO3.13 oligodendrocytes. Significant 50% to four-fold induction of alpha-synuclein protein was also detected. Under these conditions, mRNA for LXR-responsive gene ABCA1 was significantly upregulated 15-40-fold and 5-25-fold in neurons and oligodendrocytes, respectively. LXR may, therefore, contribute to the regulation of alpha-synuclein expression in neurons and oligodendrocytes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Line
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Cell Line, Tumor
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Gene Expression Regulation*
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Humans
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Hydrocarbons, Fluorinated / metabolism
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Hydrocarbons, Fluorinated / pharmacology
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Hydroxycholesterols / metabolism
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Hydroxycholesterols / pharmacology
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Ligands
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Liver X Receptors
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Neuroblastoma / genetics
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Neuroblastoma / metabolism
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Neuroblastoma / pathology
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Oligodendroglia / cytology
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Oligodendroglia / metabolism
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Orphan Nuclear Receptors
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / agonists
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Cytoplasmic and Nuclear / physiology*
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Response Elements / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Sulfonamides / metabolism
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Sulfonamides / pharmacology
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Up-Regulation / drug effects
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Up-Regulation / genetics
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alpha-Synuclein / genetics*
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alpha-Synuclein / metabolism
Substances
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DNA-Binding Proteins
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Hydrocarbons, Fluorinated
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Hydroxycholesterols
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Ligands
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Liver X Receptors
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Orphan Nuclear Receptors
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Sulfonamides
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T0901317
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alpha-Synuclein
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27-hydroxycholesterol