Reduction of Liver X Receptor 尾 expression in primary rat neurons by antisense oligodeoxynucleotides decreases secreted amyloid 尾 levels

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• 作者：Qie Wang ; Suling Wang ; Yun Shi ; Min Yao ; Lianguo Hou ; Lingling Jiang
• 关键词：ABCA1 ; ATP-binding cassette transporter A1 ; A尾 ; amyloid 尾 ; ADAM10 ; 伪-secretase ; AD ; Alzheimer's disease ; APP ; amyloid-beta precursor protein ; As-ODN ; antisense oligodeoxynucleotides ; BACE1 ; 尾-secretase ; CYP46 ; cholesterol 24-hydroxylase ; LXR ; Liver X Receptors ; HMG-CoA reductase ; 3-hydroxy-3-methylglutaryl-coenzymeA reductase
• 刊名：Neuroscience Letters
• 出版年：21 February, 2014
• 年：2014
• 卷：561
• 期：Complete
• 页码：146-150
• 全文大小：1092 K

文摘

Ligand-activated Liver X Receptor (LXR) is known to increase cholesterol efflux from cells and reduce the production of amyloid 尾 (A尾) from amyloid-beta precursor protein (APP). However, little is known about the effects of LXR尾, one subtype of LXR, on endogenous A尾. In this study, we show that LXR尾 inactivation with specific antisense oligodeoxynucleotides (As-ODN) significantly reduced secreted A尾 and decreased mRNA levels of APP_751+770, and 伪-, 尾-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 LXR尾 inactivation on A尾 levels is likely due to the alteration of cholesterol production and APP processing. Thus, our data suggest that LXR尾 has an important function in cholesterol homeostasis and endogenous A尾 maintenance in neurons.