title: Reduction of Liver X Receptor β expression in primary rat neurons by antisense oligodeoxynucleotides decreases secreted amyloid β levels.
abstract: Ligand-activated Liver X Receptor (LXR) is known to increase cholesterol efflux from cells and reduce the production of amyloid β (Aβ) from amyloid-beta precursor protein (APP). However, little is known about the effects of LXRβ, one subtype of LXR, on endogenous Aβ. In this study, we show that LXRβ inactivation with specific antisense oligodeoxynucleotides (As-ODN) significantly reduced secreted Aβ and decreased mRNA levels of APP(751+770), and α-, β-secretase (ADAM10, BACE1) in primary rat neurons. We also show that As-ODN down-regulated the LXR responsive genes ABCA1 and HMG-CoA reductase (HMGCR). These changes are associated with decreased cellular cholesterol levels. The effect of LXRβ inactivation on Aβ levels is likely due to the alteration of cholesterol production and APP processing. Thus, our data suggest that LXRβ has an important function in cholesterol homeostasis and endogenous Aβ maintenance in neurons.
authors.affiliation: Department of Anatomy, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qie
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Hebei Province Blood Center, Shijiazhuang, China.
authors.forename: Suling
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Lianguo
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, China. Electronic address: jianglingling1959@163.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Jiang
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D000072556:Cholesterol 24-Hydroxylase; D015536:Down-Regulation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D000071518:Liver X Receptors; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000378:metabolism
chemical_list: D051722:ADAM Proteins; D000072197:ADAM10 Protein; D064286:ATP Binding Cassette Transporter 1; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016282:Aspartic Acid Endopeptidases; D002784:Cholesterol; D000072556:Cholesterol 24-Hydroxylase; D006903:Hydroxymethylglutaryl CoA Reductases; D000071518:Liver X Receptors; D020319:Oligodeoxyribonucleotides, Antisense; D057093:Orphan Nuclear Receptors; D010446:Peptide Fragments; D012333:RNA, Messenger; D013250:Steroid Hydroxylases; C577834:Abca1 protein, rat; C078592:amyloid beta-protein (1-40); C509281:Bace1 protein, rat; C542371:ADAM10 protein, rat
keywords: ATP-binding cassette transporter; Alzheimer's disease; Amyloid β; Cholesterol; Liver X Receptor